34 results on '"Jos van Rijssel"'
Search Results
2. Endothelial junctional membrane protrusions serve as hotspots for neutrophil transmigration
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Janine JG Arts, Eike K Mahlandt, Max LB Grönloh, Lilian Schimmel, Ivar Noordstra, Emma Gordon, Abraham CI van Steen, Simon Tol, Barbara Walzog, Jos van Rijssel, Martijn A Nolte, Marten Postma, Satya Khuon, John M Heddleston, Eric Wait, Teng Leong Chew, Mark Winter, Eloi Montanez, Joachim Goedhart, and Jaap D van Buul
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endothelium ,Transmigration ,protrusions ,GTPase ,actin ,inflammation ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Upon inflammation, leukocytes rapidly transmigrate across the endothelium to enter the inflamed tissue. Evidence accumulates that leukocytes use preferred exit sites, alhough it is not yet clear how these hotspots in the endothelium are defined and how they are recognized by the leukocyte. Using lattice light sheet microscopy, we discovered that leukocytes prefer endothelial membrane protrusions at cell junctions for transmigration. Phenotypically, these junctional membrane protrusions are present in an asymmetric manner, meaning that one endothelial cell shows the protrusion and the adjacent one does not. Consequently, leukocytes cross the junction by migrating underneath the protruding endothelial cell. These protrusions depend on Rac1 activity and by using a photo-activatable Rac1 probe, we could artificially generate local exit-sites for leukocytes. Overall, we have discovered a new mechanism that uses local induced junctional membrane protrusions to facilitate/steer the leukocyte escape/exit from inflamed vessel walls.
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- 2021
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3. Endothelial Focal Adhesions Are Functional Obstacles for Leukocytes During Basolateral Crawling
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Janine J. G. Arts, Eike K. Mahlandt, Lilian Schimmel, Max L. B. Grönloh, Sanne van der Niet, Bart J. A. M. Klein, Mar Fernandez-Borja, Daphne van Geemen, Stephan Huveneers, Jos van Rijssel, Joachim Goedhart, and Jaap D. van Buul
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transmigration ,focal adhesions ,small GTPase ,RhoJ ,Tiam1 ,endothelium ,Immunologic diseases. Allergy ,RC581-607 - Abstract
An inflammatory response requires leukocytes to migrate from the circulation across the vascular lining into the tissue to clear the invading pathogen. Whereas a lot of attention is focused on how leukocytes make their way through the endothelial monolayer, it is less clear how leukocytes migrate underneath the endothelium before they enter the tissue. Upon finalization of the diapedesis step, leukocytes reside in the subendothelial space and encounter endothelial focal adhesions. Using TIRF microscopy, we show that neutrophils navigate around these focal adhesions. Neutrophils recognize focal adhesions as physical obstacles and deform to get around them. Increasing the number of focal adhesions by silencing the small GTPase RhoJ slows down basolateral crawling of neutrophils. However, apical crawling and diapedesis itself are not affected by RhoJ depletion. Increasing the number of focal adhesions drastically by expressing the Rac1 GEF Tiam1 make neutrophils to avoid migrating underneath these Tiam1-expressing endothelial cells. Together, our results show that focal adhesions mark the basolateral migration path of neutrophils.
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- 2021
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4. Hematopoietic stem and progenitor cells use podosomes to transcellularly cross the bone marrow endothelium
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Timo Rademakers, Marieke Goedhart, Mark Hoogenboezem, Alexander García Ponce, Jos van Rijssel, Maryna Samus, Michael Schnoor, Stefan Butz, Stephan Huveneers, Dietmar Vestweber, Martijn A. Nolte, Carlijn Voermans, and Jaap D. van Buul
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Bone marrow endothelium plays an important role in the homing of hematopoietic stem and progenitor cells upon transplantation, but surprisingly little is known on how the bone marrow endothelial cells regulate local permeability and hematopoietic stem and progenitor cells transmigration. We show that temporal loss of vascular endothelial-cadherin function promotes vascular permeability in BM, even upon low-dose irradiation. Loss of vascular endothelial-cadherin function also enhances homing of transplanted hematopoietic stem and progenitor cells to the bone marrow of irradiated mice although engraftment is not increased. Intriguingly, stabilizing junctional vascular endothelial-cadherin in vivo reduced bone marrow permeability, but did not prevent hematopoietic stem and progenitor cells migration into the bone marrow, suggesting that hematopoietic stem and progenitor cells use the transcellular migration route to enter the bone marrow. Indeed, using an in vitro migration assay, we show that human hematopoietic stem and progenitor cells predominantly cross bone marrow endothelium in a transcellular manner in homeostasis by inducing podosome-like structures. Taken together, vascular endothelial-cadherin is crucial for BM vascular homeostasis but dispensable for the homing of hematopoietic stem and progenitor cells. These findings are important in the development of potential therapeutic targets to improve hematopoietic stem and progenitor cell homing strategies.
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- 2020
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5. Stiffness-Induced Endothelial DLC-1 Expression Forces Leukocyte Spreading through Stabilization of the ICAM-1 Adhesome
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Lilian Schimmel, Miesje van der Stoel, Carmela Rianna, Anne-Marieke van Stalborch, Aafke de Ligt, Mark Hoogenboezem, Simon Tol, Jos van Rijssel, Robert Szulcek, Harm Jan Bogaard, Patrick Hofmann, Reinier Boon, Manfred Radmacher, Vivian de Waard, Stephan Huveneers, and Jaap D. van Buul
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Biology (General) ,QH301-705.5 - Abstract
Summary: Leukocytes follow the well-defined steps of rolling, spreading, and crawling prior to diapedesis through endothelial cells (ECs). We found increased expression of DLC-1 in stiffness-associated diseases like atherosclerosis and pulmonary arterial hypertension. Depletion of DLC-1 in ECs cultured on stiff substrates drastically reduced cell stiffness and mimicked leukocyte transmigration kinetics observed for ECs cultured on soft substrates. Mechanistic studies revealed that DLC-1-depleted ECs or ECs cultured on soft substrates failed to recruit the actin-adaptor proteins filamin B, α-actinin-4, and cortactin to clustered ICAM-1, thereby preventing the ICAM-1 adhesome formation and impairing leukocyte spreading. This was rescued by overexpressing DLC-1, resulting in ICAM-1 adhesome stabilization and leukocyte spreading. Our results reveal an essential role for substrate stiffness-regulated endothelial DLC-1, independent of its GAP domain, in locally stabilizing the ICAM-1 adhesome to promote leukocyte spreading, essential for efficient leukocyte transendothelial migration. : Leukocyte extravasation depends on local cellular and substrate stiffness. Schimmel et al. identified endothelial DLC-1 as a mediator to translate stiffness to leukocyte behavior. DLC-1 is crucial for the ICAM-1 adhesome, which allows leukocytes to switch from the rolling to the spreading and crawling phase, followed by diapedesis. Keywords: ICAM-1, DLC-1, spreading, leukocyte, transmigration, diapedesis, rolling, stiffness, mechanosignaling, endothelial
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- 2018
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6. The RhoGEF Trio: A Protein with a Wide Range of Functions in the Vascular Endothelium
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Lanette Kempers, Amber J. M. Driessen, Jos van Rijssel, Martijn A. Nolte, and Jaap D. van Buul
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Rho-GEF ,small GTPase ,vasculature ,endothelium ,inflammation ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Many cellular processes are controlled by small GTPases, which can be activated by guanine nucleotide exchange factors (GEFs). The RhoGEF Trio contains two GEF domains that differentially activate the small GTPases such as Rac1/RhoG and RhoA. These small RhoGTPases are mainly involved in the remodeling of the actin cytoskeleton. In the endothelium, they regulate junctional stabilization and play a crucial role in angiogenesis and endothelial barrier integrity. Multiple extracellular signals originating from different vascular processes can influence the activity of Trio and thereby the regulation of the forementioned small GTPases and actin cytoskeleton. This review elucidates how various signals regulate Trio in a distinct manner, resulting in different functional outcomes that are crucial for endothelial cell function in response to inflammation.
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- 2021
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7. Human B Cells Engage the NCK/PI3K/RAC1 Axis to Internalize Large Particles via the IgM-BCR
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Niels J. M. Verstegen, Peter-Paul A. Unger, Julia Z. Walker, Benoit P. Nicolet, Tineke Jorritsma, Jos van Rijssel, Robbert M. Spaapen, Jelle de Wit, Jaap D. van Buul, Anja ten Brinke, and S. Marieke van Ham
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B cell ,CRISPR ,internalization ,signaling pathway ,large antigen-containing particle ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Growing evidence indicate that large antigen-containing particles induce potent T cell-dependent high-affinity antibody responses. These responses require large particle internalization after recognition by the B cell receptor (BCR) on B cells. However, the molecular mechanisms governing BCR-mediated internalization remain unclear. Here we use a high-throughput quantitative image analysis approach to discriminate between B cell particle binding and internalization. We systematically show, using small molecule inhibitors, that human B cells require a SYK-dependent IgM-BCR signaling transduction via PI3K to efficiently internalize large anti-IgM-coated particles. IgM-BCR-mediated activation of PI3K involves both the adaptor protein NCK and the co-receptor CD19. Interestingly, we here reveal a strong NCK-dependence without profound requirement of the co-receptor CD19 in B cell responses to large particles. Furthermore, we demonstrate that the IgM-BCR/NCK signaling event facilitates RAC1 activation to promote actin cytoskeleton remodeling necessary for particle engulfment. Thus, we establish NCK/PI3K/RAC1 as an attractive IgM-BCR signaling axis for biological intervention to prevent undesired antibody responses to large particles.
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- 2019
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8. F-actin-rich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local RhoA signalling
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Niels Heemskerk, Lilian Schimmel, Chantal Oort, Jos van Rijssel, Taofei Yin, Bin Ma, Jakobus van Unen, Bettina Pitter, Stephan Huveneers, Joachim Goedhart, Yi Wu, Eloi Montanez, Abigail Woodfin, and Jaap D. van Buul
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Science - Abstract
Endothelial cells can support leukocyte extravasation without causing vascular leakage, but the exact mechanism underlying this process has not been fully elucidated. Here the authors show that it is regulated through actomyosin-based endothelial pore confinement, which requires local endothelial RhoA activation.
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- 2016
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9. The Rho-GEF Trio regulates a novel pro-inflammatory pathway through the transcription factor Ets2
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Jos Van Rijssel, Ilse Timmerman, Floris P. J. Van Alphen, Mark Hoogenboezem, Olexandr Korchynskyi, Dirk Geerts, Judy Geissler, Kris A. Reedquist, Hans W. M. Niessen, and Jaap D. Van Buul
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Endothelium ,GEF ,GTPase ,Inflammation ,Signal transduction ,Science ,Biology (General) ,QH301-705.5 - Abstract
Summary Inflammation is characterized by endothelium that highly expresses numerous adhesion molecules to trigger leukocyte extravasation. Central to this event is increased gene transcription. Small Rho-GTPases not only control the actin cytoskeleton, but are also implicated in gene regulation. However, in inflammation, it is not clear how this is regulated. Here, we show that the guanine-nucleotide exchange factor Trio expression is increased upon inflammatory stimuli in endothelium. Additionally, increased Trio expression was found in the vessel wall of rheumatoid arthritis patients. Trio silencing impaired VCAM-1 expression. Finally, we excluded that Trio-controlled VCAM-1 expression used the classical NFκB or MAP-kinase pathways, but rather acts on the transcriptional level by increasing phosphorylation and nuclear translocalization of Ets2. These data implicate Trio in regulating inflammation and provide novel targets for therapeutic purposes to treat inflammatory diseases such as rheumatoid arthritis.
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- 2013
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10. The N-terminal DH-PH domain of Trio induces cell spreading and migration by regulating lamellipodia dynamics in a Rac1-dependent fashion.
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Jos van Rijssel, Mark Hoogenboezem, Lynn Wester, Peter L Hordijk, and Jaap D Van Buul
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Medicine ,Science - Abstract
The guanine-nucleotide exchange factor Trio encodes two DH-PH domains that catalyze nucleotide exchange on Rac1, RhoG and RhoA. The N-terminal DH-PH domain is known to activate Rac1 and RhoG, whereas the C-terminal DH-PH domain can activate RhoA. The current study shows that the N-terminal DH-PH domain, upon expression in HeLa cells, activates Rac1 and RhoG independently from each other. In addition, we show that the flanking SH3 domain binds to the proline-rich region of the C-terminus of Rac1, but not of RhoG. However, this SH3 domain is not required for Rac1 or RhoG GDP-GTP exchange. Rescue experiments in Trio-shRNA-expressing cells showed that the N-terminal DH-PH domain of Trio, but not the C-terminal DH-PH domain, restored fibronectin-mediated cell spreading and migration defects that are observed in Trio-silenced cells. Kymograph analysis revealed that the N-terminal DH-PH domain, independent of its SH3 domain, controls the dynamics of lamellipodia. Using siRNA against Rac1 or RhoG, we found that Trio-D1-induced lamellipodia formation required Rac1 but not RhoG expression. Together, we conclude that the GEF Trio is responsible for lamellipodia formation through its N-terminal DH-PH domain in a Rac1-dependent manner during fibronectin-mediated spreading and migration.
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- 2012
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11. Inside-out regulation of ICAM-1 dynamics in TNF-alpha-activated endothelium.
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Jaap D van Buul, Jos van Rijssel, Floris P J van Alphen, Mark Hoogenboezem, Simon Tol, Kees A Hoeben, Jan van Marle, Erik P J Mul, and Peter L Hordijk
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Medicine ,Science - Abstract
BackgroundDuring transendothelial migration, leukocytes use adhesion molecules, such as ICAM-1, to adhere to the endothelium. ICAM-1 is a dynamic molecule that is localized in the apical membrane of the endothelium and clusters upon binding to leukocytes. However, not much is known about the regulation of ICAM-1 clustering and whether membrane dynamics are linked to the ability of ICAM-1 to cluster and bind leukocyte integrins. Therefore, we studied the dynamics of endothelial ICAM-1 under non-clustered and clustered conditions.Principal findingsDetailed scanning electron and fluorescent microscopy showed that the apical surface of endothelial cells constitutively forms small filopodia-like protrusions that are positive for ICAM-1 and freely move within the lateral plane of the membrane. Clustering of ICAM-1, using anti-ICAM-1 antibody-coated beads, efficiently and rapidly recruits ICAM-1. Using fluorescence recovery after photo-bleaching (FRAP), we found that clustering increased the immobile fraction of ICAM-1, compared to non-clustered ICAM-1. This shift required the intracellular portion of ICAM-1. Moreover, biochemical assays showed that ICAM-1 clustering recruited beta-actin and filamin. Cytochalasin B, which interferes with actin polymerization, delayed the clustering of ICAM-1. In addition, we could show that cytochalasin B decreased the immobile fraction of clustered ICAM-1-GFP, but had no effect on non-clustered ICAM-1. Also, the motor protein myosin-II is recruited to ICAM-1 adhesion sites and its inhibition increased the immobile fraction of both non-clustered and clustered ICAM-1. Finally, blocking Rac1 activation, the formation of lipid rafts, myosin-II activity or actin polymerization, but not Src, reduced the adhesive function of ICAM-1, tested under physiological flow conditions.ConclusionsTogether, these findings indicate that ICAM-1 clustering is regulated in an inside-out fashion through the actin cytoskeleton. Overall, these data indicate that signaling events within the endothelium are required for efficient ICAM-1-mediated leukocyte adhesion.
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- 2010
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12. Author response: Endothelial junctional membrane protrusions serve as hotspots for neutrophil transmigration
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Emma Gordon, Eike K. Mahlandt, Jos van Rijssel, Mark R. Winter, Simon Tol, Ivar Noordstra, Marten Postma, Janine J. G. Arts, Abraham C.I. van Steen, Eric Wait, Joachim Goedhart, Martijn A. Nolte, Eloi Montanez, Lilian Schimmel, Teng Leong Chew, Max L. B. Grönloh, Satya Khuon, John M. Heddleston, Jaap D. van Buul, and Barbara Walzog
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Membrane ,Chemistry ,Cell biology - Published
- 2021
13. Endothelial junctional membrane protrusions serve as hotspots for neutrophil transmigration
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Simon Tol, John M. Heddleston, Barbara Walzog, Eric Wait, Ivar Noordstra, Eloi Montanez, Marten Postma, Abraham C.I. van Steen, Joachim Goedhart, Lilian Schimmel, Martijn A. Nolte, Teng-Leong Chew, Mark R. Winter, Emma Gordon, Eike K. Mahlandt, Jos van Rijssel, Max L. B. Grönloh, Janine J. G. Arts, Jaap D. van Buul, Satya Khuon, Landsteiner Laboratory, Graduate School, AII - Inflammatory diseases, AII - Infectious diseases, ACS - Atherosclerosis & ischemic syndromes, SILS Other Research (FNWI), and Molecular Cytology (SILS, FNWI)
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Male ,Mouse ,Small GTPase ,Neutrophils ,Cell junction ,Mice ,Immunology and Inflammation ,Immunologia ,Biology (General) ,Leucòcits ,Chemistry ,General Neuroscience ,General Medicine ,protrusions ,Inflamació ,Cell biology ,Endothelial stem cell ,Membrane ,medicine.anatomical_structure ,Intercellular Junctions ,Transmigration ,Medicine ,medicine.symptom ,actin ,Rac1 ,Research Article ,Human ,Endothelium ,endothelium ,QH301-705.5 ,Science ,Green Fluorescent Proteins ,Immunology ,RAC1 ,Inflammation ,Mice, Transgenic ,Endoteli ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Microscopy, Electron, Transmission ,medicine ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,Muscle, Skeletal ,Leucocytes ,GTPase ,Actin ,General Immunology and Microbiology ,Cell Biology ,Gene Expression Regulation ,inflammation - Abstract
Upon inflammation, leukocytes rapidly transmigrate across the endothelium to enter the inflamed tissue. Evidence accumulates that leukocytes use preferred exit sites, alhough it is not yet clear how these hotspots in the endothelium are defined and how they are recognized by the leukocyte. Using lattice light sheet microscopy, we discovered that leukocytes prefer endothelial membrane protrusions at cell junctions for transmigration. Phenotypically, these junctional membrane protrusions are present in an asymmetric manner, meaning that one endothelial cell shows the protrusion and the adjacent one does not. Consequently, leukocytes cross the junction by migrating underneath the protruding endothelial cell. These protrusions depend on Rac1 activity and by using a photo-activatable Rac1 probe, we could artificially generate local exit-sites for leukocytes. Overall, we have discovered a new mechanism that uses local induced junctional membrane protrusions to facilitate/steer the leukocyte escape/exit from inflamed vessel walls.
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- 2021
14. Endothelial junctional membrane protrusions serve as hotspots for neutrophil transmigration
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Satya Khuon, Teng-Leong Chew, Abraham C.I. van Steen, Simon Tol, Mark R. Winter, Lilian Schimmel, Ivar Noordstra, Jos van Rijssel, Marten Postma, Joachim Goedhart, Martijn A. Nolte, Eloi Montanez, John M. Heddleston, Eric Wait, Max L. B. Grönloh, Eike K. Mahlandt, Jaap D. van Buul, and Janine J. G. Arts
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Endothelial stem cell ,medicine.anatomical_structure ,Membrane ,Endothelium ,Chemistry ,medicine ,Inflammation ,RAC1 ,medicine.symptom ,Cell junction ,Cell biology - Abstract
Upon inflammation, leukocytes rapidly transmigrate across the endothelium to enter the inflamed tissue. Evidence accumulates that leukocytes use preferred exit sites, though it is not yet clear how these hotspots in the endothelium are defined and how they are recognized by the leukocyte. Using lattice light sheet microscopy, we discovered that leukocytes prefer endothelial membrane protrusions at cell junctions for transmigration. Phenotypically, these junctional membrane protrusions are present in an asymmetric manner, meaning that one endothelial cell shows the protrusion and the adjacent one does not. Consequently, leukocytes cross the junction by migrating underneath the protruding endothelial cell. These protrusions depend on Rac1 activity and by using a photo-activatable Rac1 probe, we could artificially generate local exit-sites for leukocytes. Overall, we have discovered a new mechanism that uses local induced junctional membrane protrusions to facilitate/steer the leukocyte escape/exit from inflamed vessel walls.
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- 2021
15. Long non-coding RNA LASSIE regulates shear stress sensing and endothelial barrier function
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Noelia Lozano-Vidal, Jaap D. van Buul, Stefan Offermanns, Alina Klems, Wenjie Yao, Diewertje I. Bink, Ferdinand le Noble, Meryem S. Ercanoglu, Leo Kurian, Reinier Abraham Boon, Stephan Huveneers, Shengpeng Wang, Robert Szulcek, Anke van Bergen, Hyouk Bum Kwon, Aukie Hooglugt, Stefanie Dimmeler, Didier Y.R. Stainier, Ilka Wittig, Laura Stanicek, Patrick Hofmann, Anne Sophie Ramms, Jos van Rijssel, Physiology, ACS - Microcirculation, Pulmonary medicine, ACS - Atherosclerosis & ischemic syndromes, Landsteiner Laboratory, and Medical Biochemistry
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Life sciences ,biology ,0301 basic medicine ,Cell ,Medicine (miscellaneous) ,macromolecular substances ,030204 cardiovascular system & hematology ,General Biochemistry, Genetics and Molecular Biology ,Article ,Adherens junction ,03 medical and health sciences ,0302 clinical medicine ,ddc:570 ,medicine ,Shear stress ,Human Umbilical Vein Endothelial Cells ,Intermediate Filament Protein ,Adherens junctions ,Humans ,Cytoskeleton ,lcsh:QH301-705.5 ,Barrier function ,Chemistry ,RNA ,Endothelial Cells ,Nestin ,Cardiovascular biology ,Cell biology ,Biomechanical Phenomena ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,Long non-coding RNAs ,RNA, Long Noncoding ,Stress, Mechanical ,General Agricultural and Biological Sciences - Abstract
Blood vessels are constantly exposed to shear stress, a biomechanical force generated by blood flow. Normal shear stress sensing and barrier function are crucial for vascular homeostasis and are controlled by adherens junctions (AJs). Here we show that AJs are stabilized by the shear stress-induced long non-coding RNA LASSIE (linc00520). Silencing of LASSIE in endothelial cells impairs cell survival, cell-cell contacts and cell alignment in the direction of flow. LASSIE associates with junction proteins (e.g. PECAM-1) and the intermediate filament protein nestin, as identified by RNA affinity purification. The AJs component VE-cadherin showed decreased stabilization, due to reduced interaction with nestin and the microtubule cytoskeleton in the absence of LASSIE. This study identifies LASSIE as link between nestin and VE-cadherin, and describes nestin as crucial component in the endothelial response to shear stress. Furthermore, this study indicates that LASSIE regulates barrier function by connecting AJs to the cytoskeleton., Stanicek et al identify a shear stress-induced long non-coding RNA they name LASSIE, which stabilises junctions between endothelial cells through interactions with junctional and cytoskeletal proteins. This study provides insights into how a transcript that does not encode a protein controls endothelial response to forces associated with blood flow and endothelial barrier function.
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- 2020
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16. Stiffness-Induced Endothelial DLC-1 Expression Forces Leukocyte Spreading through Stabilization of the ICAM-1 Adhesome
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Simon Tol, Mark Hoogenboezem, Patrick Hofmann, Aafke de Ligt, Robert Szulcek, Reinier A. Boon, Anne-Marieke D. van Stalborch, Carmela Rianna, Harm Jan Bogaard, Jaap D. van Buul, Lilian Schimmel, Stephan Huveneers, Jos van Rijssel, Manfred Radmacher, Miesje M. van der Stoel, Vivian de Waard, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Physiology, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, Graduate School, Landsteiner Laboratory, and Medical Biochemistry
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0301 basic medicine ,Leukocyte transendothelial migration ,animal structures ,macromolecular substances ,Filamin ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Mediator ,Vascular Stiffness ,Substrate stiffness ,Human Umbilical Vein Endothelial Cells ,Leukocytes ,Humans ,lcsh:QH301-705.5 ,Cells, Cultured ,ICAM-1 ,biology ,Adhesome ,Chemistry ,Tumor Suppressor Proteins ,GTPase-Activating Proteins ,Microfilament Proteins ,Transendothelial and Transepithelial Migration ,Intercellular Adhesion Molecule-1 ,Leukocyte extravasation ,Cell biology ,030104 developmental biology ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,biology.protein ,Cortactin - Abstract
Summary: Leukocytes follow the well-defined steps of rolling, spreading, and crawling prior to diapedesis through endothelial cells (ECs). We found increased expression of DLC-1 in stiffness-associated diseases like atherosclerosis and pulmonary arterial hypertension. Depletion of DLC-1 in ECs cultured on stiff substrates drastically reduced cell stiffness and mimicked leukocyte transmigration kinetics observed for ECs cultured on soft substrates. Mechanistic studies revealed that DLC-1-depleted ECs or ECs cultured on soft substrates failed to recruit the actin-adaptor proteins filamin B, α-actinin-4, and cortactin to clustered ICAM-1, thereby preventing the ICAM-1 adhesome formation and impairing leukocyte spreading. This was rescued by overexpressing DLC-1, resulting in ICAM-1 adhesome stabilization and leukocyte spreading. Our results reveal an essential role for substrate stiffness-regulated endothelial DLC-1, independent of its GAP domain, in locally stabilizing the ICAM-1 adhesome to promote leukocyte spreading, essential for efficient leukocyte transendothelial migration. : Leukocyte extravasation depends on local cellular and substrate stiffness. Schimmel et al. identified endothelial DLC-1 as a mediator to translate stiffness to leukocyte behavior. DLC-1 is crucial for the ICAM-1 adhesome, which allows leukocytes to switch from the rolling to the spreading and crawling phase, followed by diapedesis. Keywords: ICAM-1, DLC-1, spreading, leukocyte, transmigration, diapedesis, rolling, stiffness, mechanosignaling, endothelial
- Published
- 2018
17. The RhoGEF Trio: A Protein with a Wide Range of Functions in the Vascular Endothelium
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Martijn A. Nolte, Jos van Rijssel, Jaap D. van Buul, Amber J. M. Driessen, and Lanette Kempers
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vasculature ,RHOA ,endothelium ,QH301-705.5 ,Angiogenesis ,RAC1 ,Review ,GTPase ,Protein Serine-Threonine Kinases ,Catalysis ,Inorganic Chemistry ,Animals ,Humans ,Small GTPase ,Biology (General) ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Spectroscopy ,biology ,Chemistry ,Organic Chemistry ,General Medicine ,Actin cytoskeleton ,Computer Science Applications ,Cell biology ,Rho-GEF ,small GTPase ,inflammation ,biology.protein ,Endothelium, Vascular ,Guanine nucleotide exchange factor ,RhoG ,rhoA GTP-Binding Protein ,Signal Transduction - Abstract
Many cellular processes are controlled by small GTPases, which can be activated by guanine nucleotide exchange factors (GEFs). The RhoGEF Trio contains two GEF domains that differentially activate the small GTPases such as Rac1/RhoG and RhoA. These small RhoGTPases are mainly involved in the remodeling of the actin cytoskeleton. In the endothelium, they regulate junctional stabilization and play a crucial role in angiogenesis and endothelial barrier integrity. Multiple extracellular signals originating from different vascular processes can influence the activity of Trio and thereby the regulation of the forementioned small GTPases and actin cytoskeleton. This review elucidates how various signals regulate Trio in a distinct manner, resulting in different functional outcomes that are crucial for endothelial cell function in response to inflammation.
- Published
- 2021
18. Role of glutamine synthetase in angiogenesis beyond glutamine synthesis
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Christian Lange, Johan Hofkens, Sandra Liekens, Hongling Huang, Xu Wu, Joris Souffreau, Giorgio Saladino, Guy Eelen, Jaap D. van Buul, Saar Vandekeere, Wouter H. Lamers, Xuri Li, Gopala K. Jarugumilli, Federico Comitani, Annalisa Zecchin, Jermaine Goveia, Bert Cruys, Katleen Brepoels, Joanna Kalucka, Bart Ghesquière, Leanne M. Ramer, Ulrike Bruning, Michael DeRan, Charlotte Dubois, Francesco Luigi Gervasio, Jos van Rijssel, Stefan Vinckier, Sabine Wyns, Yi I. Wu, Mieke Dewerchin, Francisco Morales-Rodriguez, Susana Rocha, Rongyuan Chen, Richard M Cubbon, Luc Schoonjans, Lucas Treps, Peter Carmeliet, Anna Rita Cantelmo, Jurgen Haustraete, Landsteiner Laboratory, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and Tytgat Institute for Liver and Intestinal Research
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0301 basic medicine ,rho GTP-Binding Proteins ,Angiogenesis ,MIGRATION ,GLYCOLYSIS ,Glutamine ,Lipoylation ,Palmitic Acid ,PATHWAY ,03 medical and health sciences ,Mice ,RHO GTPASE ,Palmitoylation ,Cell Movement ,Glutamate-Ammonia Ligase ,Glutamine synthetase ,Stress Fibers ,VASCULATURE ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,Protein palmitoylation ,Rho-associated protein kinase ,rho-Associated Kinases ,Multidisciplinary ,Science & Technology ,Neovascularization, Pathologic ,Chemistry ,HEK 293 cells ,Endothelial Cells ,JUNCTIONS ,ENDOTHELIAL-CELLS ,Actins ,Cell biology ,Endothelial stem cell ,Multidisciplinary Sciences ,DEFICIENCY ,MODEL ,030104 developmental biology ,HEK293 Cells ,Science & Technology - Other Topics ,Female ,PROTEIN PALMITOYLATION ,Protein Processing, Post-Translational - Abstract
Glutamine synthetase, encoded by the gene GLUL, is an enzyme that converts glutamate and ammonia to glutamine. It is expressed by endothelial cells, but surprisingly shows negligible glutamine-synthesizing activity in these cells at physiological glutamine levels. Here we show in mice that genetic deletion of Glul in endothelial cells impairs vessel sprouting during vascular development, whereas pharmacological blockade of glutamine synthetase suppresses angiogenesis in ocular and inflammatory skin disease while only minimally affecting healthy adult quiescent endothelial cells. This relies on the inhibition of endothelial cell migration but not proliferation. Mechanistically we show that in human umbilical vein endothelial cells GLUL knockdown reduces membrane localization and activation of the GTPase RHOJ while activating other Rho GTPases and Rho kinase, thereby inducing actin stress fibres and impeding endothelial cell motility. Inhibition of Rho kinase rescues the defect in endothelial cell migration that is induced by GLUL knockdown. Notably, glutamine synthetase palmitoylates itself and interacts with RHOJ to sustain RHOJ palmitoylation, membrane localization and activation. These findings reveal that, in addition to the known formation of glutamine, the enzyme glutamine synthetase shows unknown activity in endothelial cell migration during pathological angiogenesis through RHOJ palmitoylation. ispartof: NATURE vol:561 issue:7721 pages:63-+ ispartof: location:England status: published
- Published
- 2018
19. Inflammation-sensitive myosin-x functionally supports leukocyte extravasation by Cdc42-mediated ICAM-1-rich endothelial filopodia formation
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Erik S.G. Stroes, Jacco van Rheenen, Antje Schaefer, Jeffrey Kroon, Floris P. J. van Alphen, Staffan Strömblad, Mark Hoogenboezem, Peter L. Hordijk, Jos van Rijssel, Jaap D. van Buul, AII - Inflammatory diseases, AII - Amsterdam institute for Infection and Immunity, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Landsteiner Laboratory, Other departments, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, and Physiology
- Subjects
Endothelium ,Immunology ,Inflammation ,HL-60 Cells ,CDC42 ,Myosins ,Cell Line ,GTP Phosphohydrolases ,Cell Line, Tumor ,Myosin ,medicine ,Cell Adhesion ,Human Umbilical Vein Endothelial Cells ,Leukocytes ,Immunology and Allergy ,Humans ,Pseudopodia ,Kinase activity ,ICAM-1 ,Chemistry ,Transendothelial and Transepithelial Migration ,Endothelial Cells ,Intercellular Adhesion Molecule-1 ,Leukocyte extravasation ,Actins ,Cell biology ,Up-Regulation ,medicine.anatomical_structure ,Endothelium, Vascular ,medicine.symptom ,Filopodia ,HeLa Cells ,Signal Transduction - Abstract
Leukocyte transendothelial migration is key to inflammation. Leukocytes first start rolling over the inflamed endothelium, followed by firmly adhering to it. Under inflammatory conditions, endothelial cells express small finger-like protrusions that stick out into the lumen. The function and regulation of these structures are unclear. We present evidence that these ICAM-1– and F-actin–rich endothelial finger-like protrusions are filopodia and function as adhesive structures for leukocytes to transit from rolling to crawling but are dispensable for diapedesis. Mechanistically, these structures require the motor function of myosin-X, activity of the small GTPase Cdc42, and p21-activated kinase 4. Moreover, myosin-X expression is under control of TNF-α–mediated c-Jun N-terminal kinase activity and is upregulated in human atherosclerotic regions. To our knowledge, this is the first study to identify that regulation of endothelial filopodia is crucial for leukocyte extravasation, in particular for the initiation of leukocyte adhesion under flow conditions.
- Published
- 2018
20. Flow-induced endothelial cell alignment requires the RhoGEF Trio as a scaffold protein to polarize active Rac1 distribution
- Author
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Niels Heemskerk, Jos van Rijssel, Vivian de Waard, Martin J. T. Kalsbeek, Jaap D. van Buul, Jeffrey Kroon, Other departments, ACS - Atherosclerosis & ischemic syndromes, Medical Biochemistry, Landsteiner Laboratory, Amsterdam Gastroenterology Endocrinology Metabolism, and ACS - Microcirculation
- Subjects
rac1 GTP-Binding Protein ,0301 basic medicine ,Scaffold protein ,Cell Physiology ,Cell ,RAC1 ,Protein Serine-Threonine Kinases ,Biology ,03 medical and health sciences ,Human Umbilical Vein Endothelial Cells ,medicine ,Humans ,Small GTPase ,Molecular Biology ,Cells, Cultured ,Endothelial Cells ,Articles ,Cell Biology ,Phosphoproteins ,Actin cytoskeleton ,Actins ,Cell biology ,Endothelial stem cell ,Actin Cytoskeleton ,030104 developmental biology ,medicine.anatomical_structure ,Förster resonance energy transfer ,Hydrodynamics ,Rho Guanine Nucleotide Exchange Factors ,Signal Transduction ,Lumen (unit) - Abstract
Long-term flow conditions promote endothelial cells to align in the direction of flow. The endothelial RhoGEF Trio keeps active Rac1 at the downstream side rather than exchanging GTP. Thus Trio acts as a scaffold protein to regulate endothelial cell polarization under long-term flow conditions., Endothelial cells line the lumen of the vessel wall and are exposed to flow. In linear parts of the vessel, the endothelial cells experience laminar flow, resulting in endothelial cell alignment in the direction of flow, thereby protecting the vessel wall from inflammation and permeability. In order for endothelial cells to align, they undergo rapid remodeling of the actin cytoskeleton by local activation of the small GTPase Rac1. However, it is not clear whether sustained and local activation of Rac1 is required for long-term flow-induced cell alignment. Using a FRET-based DORA Rac1 biosensor, we show that local Rac1 activity remains for 12 h upon long-term flow. Silencing studies show that the RhoGEF Trio is crucial for keeping active Rac1 at the downstream side of the cell and, as a result, for long-term flow-induced cell alignment. Surprisingly, Trio appears to be not involved in flow-induced activation of Rac1. Our data show that flow induces Rac1 activity at the downstream side of the cell in a Trio-dependent manner and that Trio functions as a scaffold protein rather than a functional GEF under long-term flow conditions.
- Published
- 2017
21. Rho-GTPase signaling in leukocyte extravasation
- Author
-
Niels Heemskerk, Jos van Rijssel, and Jaap D. van Buul
- Subjects
Cellular and Molecular Neuroscience ,biology ,Cell adhesion molecule ,Integrin ,Intercellular Adhesion Molecule-1 ,biology.protein ,Cell Biology ,Apical membrane ,Signal transduction ,Cell adhesion ,Leukocyte extravasation ,Extravasation ,Cell biology - Abstract
Leukocyte transendothelial migration (TEM) is one of the crucial steps during inflammation. A better understanding of the key molecules that regulate leukocyte extravasation aids to the development of novel therapeutics for treatment of inflammation-based diseases, such as atherosclerosis and rheumatoid arthritis. The adhesion molecules ICAM-1 and VCAM-1 are known as central mediators of TEM. Clustering of these molecules by their leukocytic integrins initiates the activation of several signaling pathways within the endothelium, including a rise in intracellular Ca (2+), activation of several kinase cascades, and the activation of Rho-GTPases. Activation of Rho-GTPases has been shown to control adhesion molecule clustering and the formation of apical membrane protrusions that embrace adherent leukocytes during TEM. Here, we discuss the potential regulatory mechanisms of leukocyte extravasation from an endothelial point of view, with specific focus on the role of the Rho-GTPases
- Published
- 2014
22. The Rho-GEF Trio regulates a novel pro-inflammatory pathway through the transcription factor Ets2
- Author
-
Mark Hoogenboezem, Ilse Timmerman, Hans W.M. Niessen, Floris P. J. van Alphen, Kris A. Reedquist, Olexandr Korchynskyi, Jaap D. van Buul, Judy Geissler, Jos van Rijssel, Dirk Geerts, Hematology laboratory, Pathology, ICaR - Heartfailure and pulmonary arterial hypertension, ICaR - Ischemia and repair, Clinical Immunology and Rheumatology, Other departments, Amsterdam institute for Infection and Immunity, Experimental Immunology, and Landsteiner Laboratory
- Subjects
Regulation of gene expression ,Inflammation ,QH301-705.5 ,Cell adhesion molecule ,Science ,Biology ,Signal transduction ,Actin cytoskeleton ,Leukocyte extravasation ,General Biochemistry, Genetics and Molecular Biology ,Cell biology ,Immunology ,medicine ,Gene silencing ,Endothelium ,Biology (General) ,medicine.symptom ,GEF ,General Agricultural and Biological Sciences ,Transcription factor ,GTPase ,Research Article - Abstract
Summary Inflammation is characterized by endothelium that highly expresses numerous adhesion molecules to trigger leukocyte extravasation. Central to this event is increased gene transcription. Small Rho-GTPases not only control the actin cytoskeleton, but are also implicated in gene regulation. However, in inflammation, it is not clear how this is regulated. Here, we show that the guanine-nucleotide exchange factor Trio expression is increased upon inflammatory stimuli in endothelium. Additionally, increased Trio expression was found in the vessel wall of rheumatoid arthritis patients. Trio silencing impaired VCAM-1 expression. Finally, we excluded that Trio-controlled VCAM-1 expression used the classical NFκB or MAP-kinase pathways, but rather acts on the transcriptional level by increasing phosphorylation and nuclear translocalization of Ets2. These data implicate Trio in regulating inflammation and provide novel targets for therapeutic purposes to treat inflammatory diseases such as rheumatoid arthritis.
- Published
- 2013
23. Annexin A2 Limits Neutrophil Transendothelial Migration by Organizing the Spatial Distribution of ICAM-1
- Author
-
Jos van Rijssel, Chantal Oort, Niels Heemskerk, Mohammed Asimuddin, Jaap D. van Buul, Landsteiner Laboratory, and CCA - Immuno-pathogenesis
- Subjects
0301 basic medicine ,Endothelium ,Neutrophils ,Immunology ,Intercellular Adhesion Molecule-1 ,Caveolin 1 ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,medicine ,Cell Adhesion ,Human Umbilical Vein Endothelial Cells ,Leukocytes ,Immunology and Allergy ,Humans ,Cell adhesion ,Annexin A2 ,ICAM-1 ,Receptor Aggregation ,Transendothelial and Transepithelial Migration ,Endothelial Cells ,Adhesion ,Transport protein ,Cell biology ,Protein Transport ,030104 developmental biology ,medicine.anatomical_structure ,030215 immunology ,Protein Binding - Abstract
ICAM-1 is required for firm adhesion of leukocytes to the endothelium. However, how the spatial organization of endothelial ICAM-1 regulates leukocyte adhesion is not well understood. In this study, we identified the calcium-effector protein annexin A2 as a novel binding partner for ICAM-1. ICAM-1 clustering promotes the ICAM-1–annexin A2 interaction and induces translocation of ICAM-1 into caveolin-1–rich membrane domains. Depletion of endothelial annexin A2 using RNA interference enhances ICAM-1 membrane mobility and prevents the translocation of ICAM-1 into caveolin-1–rich membrane domains. Surprisingly, this results in increased neutrophil adhesion and transendothelial migration under flow conditions and reduced crawling time, velocity, and lateral migration distance of neutrophils on the endothelium. In conclusion, our data show that annexin A2 limits neutrophil transendothelial migration by organizing the spatial distribution of ICAM-1.
- Published
- 2016
24. F-actin-rich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local RhoA signalling
- Author
-
Abigail Woodfin, Taofei Yin, Yi I. Wu, Niels Heemskerk, Stephan Huveneers, Jaap D. van Buul, Jos van Rijssel, Bin Ma, Jakobus van Unen, Eloi Montanez, Lilian Schimmel, Bettina Pitter, Joachim Goedhart, Chantal Oort, Molecular Cytology (SILS, FNWI), CCA - Immuno-pathogenesis, Medical Biochemistry, Landsteiner Laboratory, AII - Amsterdam institute for Infection and Immunity, and ACS - Amsterdam Cardiovascular Sciences
- Subjects
0301 basic medicine ,Cellular signal transduction ,RHOA ,Endothelium ,Neutrophils ,Science ,Intercellular Adhesion Molecule-1 ,General Physics and Astronomy ,Vascular permeability ,Epithelial cells ,General Biochemistry, Genetics and Molecular Biology ,Article ,Capillary Permeability ,03 medical and health sciences ,Mice ,Vascular endothelial growth factors ,medicine ,Human Umbilical Vein Endothelial Cells ,Leukocytes ,Animals ,Humans ,ROCK1 ,Cytoskeleton ,Cells, Cultured ,Cèl·lules epitelials ,Multidisciplinary ,biology ,Factor de creixement de l'endoteli vascular ,Transendothelial and Transepithelial Migration ,Transducció de senyal cel·lular ,General Chemistry ,Actin cytoskeleton ,Leukocyte extravasation ,Metabolisme ,Actins ,Cell biology ,Mice, Inbred C57BL ,Actin Cytoskeleton ,030104 developmental biology ,medicine.anatomical_structure ,Metabolism ,biology.protein ,Endothelium, Vascular ,rhoA GTP-Binding Protein ,Signal Transduction - Abstract
During immune surveillance and inflammation, leukocytes exit the vasculature through transient openings in the endothelium without causing plasma leakage. However, the exact mechanisms behind this intriguing phenomenon are still unknown. Here we report that maintenance of endothelial barrier integrity during leukocyte diapedesis requires local endothelial RhoA cycling. Endothelial RhoA depletion in vitro or Rho inhibition in vivo provokes neutrophil-induced vascular leakage that manifests during the physical movement of neutrophils through the endothelial layer. Local RhoA activation initiates the formation of contractile F-actin structures that surround emigrating neutrophils. These structures that surround neutrophil-induced endothelial pores prevent plasma leakage through actomyosin-based pore confinement. Mechanistically, we found that the initiation of RhoA activity involves ICAM-1 and the Rho GEFs Ect2 and LARG. In addition, regulation of actomyosin-based endothelial pore confinement involves ROCK2b, but not ROCK1. Thus, endothelial cells assemble RhoA-controlled contractile F-actin structures around endothelial pores that prevent vascular leakage during leukocyte extravasation., Endothelial cells can support leukocyte extravasation without causing vascular leakage, but the exact mechanism underlying this process has not been fully elucidated. Here the authors show that it is regulated through actomyosin-based endothelial pore confinement, which requires local endothelial RhoA activation.
- Published
- 2016
25. The many faces of the guanine-nucleotide exchange factor trio
- Author
-
Jos van Rijssel, Jaap D. van Buul, and Landsteiner Laboratory
- Subjects
rac1 GTP-Binding Protein ,RHOA ,animal structures ,GTP' ,Neurogenesis ,RAC1 ,GTPase ,Biology ,Protein Serine-Threonine Kinases ,environment and public health ,src Homology Domains ,Cellular and Molecular Neuroscience ,GTP-binding protein regulators ,Cell Movement ,Cell Line, Tumor ,Protein Interaction Mapping ,Leukocytes ,Animals ,Guanine Nucleotide Exchange Factors ,Humans ,Nucleotide ,Pseudopodia ,Phosphorylation ,chemistry.chemical_classification ,fungi ,Cell Biology ,Cell biology ,RhoG ,Enzyme Activation ,Gene Expression Regulation, Neoplastic ,enzymes and coenzymes (carbohydrates) ,Rho-GEF ,chemistry ,Trio ,lamellipodia ,biology.protein ,Commentary ,Guanine nucleotide exchange factor ,biological phenomena, cell phenomena, and immunity ,Rac1 - Abstract
Small Rho-GTPases are enzymes that are bound to GDP or GTP, which determines their inactive or active state, respectively. The exchange of GDP for GTP is catalyzed by so-called Rho-guanine nucleotide exchange factors (GEFs). Rho-GEFs are characterized by a Dbl-homology (DH) and adjacent Pleckstrin-homology (PH) domain that serves as enzymatic unit for the GDP/GTP exchange. Rho-GEFs show different GTPase specificities, meaning that a particular GEF can activate either multiple GTPases or only one specific GTPase. We recently reported that the Rho-GEF Trio, known to be able to exchange GTP on Rac1, RhoG and RhoA, regulates lamellipodia formation to mediate cell spreading and migration in a Rac1-dependent manner. In this commentary, we review the current knowledge of Trio in several aspects of cell biology.
- Published
- 2012
26. Tunable Dual Emission in Doped Semiconductor Nanocrystals
- Author
-
Vladimir A. Vlaskin, Daniel R. Gamelin, Jos van Rijssel, Rémi Beaulac, and Nils Janssen
- Subjects
Materials science ,Condensed Matter::Other ,business.industry ,Band gap ,Mechanical Engineering ,Dual emission ,Doping ,Physics::Optics ,Bioengineering ,Nanotechnology ,General Chemistry ,Condensed Matter::Mesoscopic Systems and Quantum Hall Effect ,Condensed Matter Physics ,Photoexcitation ,Condensed Matter::Materials Science ,Colloid ,Nanocrystal ,Excited state ,Physics::Atomic and Molecular Clusters ,Optoelectronics ,General Materials Science ,Luminescence ,business - Abstract
Colloidal manganese-doped semiconductor nanocrystals have been developed that show pronounced intrinsic high-temperature dual emission. Photoexcitation of these nanocrystals gives rise to strongly temperature dependent luminescence involving two distinct but interconnected emissive excited states of the same doped nanocrystals. The ratio of the two intensities is independent of nonradiative effects. The temperature window over which pronounced dual emission is observed can be tuned by changing the nanocrystal energy gap during growth. This unique combination of properties makes this new class of intrinsic dual emitters attractive for ratiometric optical thermometry applications.
- Published
- 2010
27. Filamin B Mediates ICAM-1-driven Leukocyte Transendothelial Migration
- Author
-
Arnoud Sonnenberg, Paul J. Hensbergen, Jos van Rijssel, Peter L. Hordijk, David Hondius, Frederik P. J. Mul, André M. Deelder, Jaap D. van Buul, Edwin Kanters, Pathology, Physiology, and Landsteiner Laboratory
- Subjects
Small interfering RNA ,animal structures ,Endothelium ,Filamins ,Caveolin 1 ,Endogeny ,Inflammation ,macromolecular substances ,Biology ,Filamin ,Biochemistry ,Contractile Proteins ,Cell Movement ,Genes, Reporter ,Chlorocebus aethiops ,medicine ,Leukocytes ,Animals ,Humans ,Molecular Biology ,Actin ,Cells, Cultured ,ICAM-1 ,Microfilament Proteins ,Endothelial Cells ,Cell Biology ,Intercellular Adhesion Molecule-1 ,Cell biology ,body regions ,medicine.anatomical_structure ,medicine.symptom ,Intracellular ,Protein Binding - Abstract
During inflammation, the endothelium mediates rolling and firm adhesion of activated leukocytes. Integrin-mediated adhesion to endothelial ligands of the Ig-superfamily induces intracellular signaling in endothelial cells, which promotes leukocyte transendothelial migration. We identified the actin cross-linking molecule filamin B as a novel binding partner for intracellular adhesion molecule-1 (ICAM-1). Immune precipitation as well as laser scanning confocal microscopy confirmed the specific interaction and co-localization of endogenous filamin B with ICAM-1. Importantly, clustering of ICAM-1 promotes the ICAM-1-filamin B interaction. To investigate the functional consequences of filamin B binding to ICAM-1, we used small interfering RNA to reduce filamin B expression in ICAM-1-GFP expressing HeLa cells. We found that filamin B is required for the lateral mobility of ICAM-1 and for ICAM-1-induced transmigration of leukocytes. Reducing filamin B expression in primary human endothelial cells resulted in reduced recruitment of ICAM-1 to endothelial docking structures, reduced firm adhesion of the leukocytes to the endothelium, and inhibition of transendothelial migration. In conclusion, this study identifies filamin B as a molecular linker that mediates ICAM-1-driven transendothelial migration.
- Published
- 2008
28. The Rho-guanine nucleotide exchange factor Trio controls leukocyte transendothelial migration by promoting docking structure formation
- Author
-
Mark Hoogenboezem, Jeffrey Kroon, Jaap D. van Buul, Dirk Geerts, Renske J. de Jong, Peter L. Hordijk, Elena Kostadinova, Jos van Rijssel, Floris P. J. van Alphen, Physiology, Landsteiner Laboratory, Other departments, and Hematology laboratory
- Subjects
rac1 GTP-Binding Protein ,rho GTP-Binding Proteins ,Filamins ,Intercellular Adhesion Molecule-1 ,RAC1 ,Biology ,Protein Serine-Threonine Kinases ,Nucleotide exchange factor ,SGEF ,Contractile Proteins ,Chlorocebus aethiops ,Cell Adhesion ,Electric Impedance ,Leukocytes ,Animals ,Guanine Nucleotide Exchange Factors ,Humans ,Cell Interactions ,Cell adhesion ,Molecular Biology ,Microfilament Proteins ,Transendothelial and Transepithelial Migration ,Cell Biology ,Articles ,Apical membrane ,Cell biology ,Protein Structure, Tertiary ,HEK293 Cells ,Cell Tracking ,COS Cells ,Guanine nucleotide exchange factor ,RhoG ,HeLa Cells - Abstract
Neutrophils induce endothelial docking structures prior to crossing the blood vessel wall. The Rho guanine nucleotide exchange factor Trio regulates the formation of these structures through ICAM-1 clustering in a filamin-dependent fashion. We show that Trio is a crucial mediator of the signaling pathway that controls leukocyte extravasation through docking structure formation., Leukocyte transendothelial migration involves the active participation of the endothelium through the formation of apical membrane protrusions that embrace adherent leukocytes, termed docking structures. Using live-cell imaging, we find that prior to transmigration, endothelial docking structures form around 80% of all neutrophils. Previously we showed that endothelial RhoG and SGEF control leukocyte transmigration. In this study, our data reveal that both full-length Trio and the first DH-PH (TrioD1) domain of Trio, which can activate Rac1 and RhoG, interact with ICAM-1 and are recruited to leukocyte adhesion sites. Moreover, upon clustering of ICAM-1, the Rho-guanine nucleotide exchange factor Trio activates Rac1, prior to activating RhoG, in a filamin-dependent manner. We further show that docking structure formation is initiated by ICAM-1 clustering into ring-like structures, which is followed by apical membrane protrusion. Interestingly, we find that Rac1 is required for ICAM-1 clustering, whereas RhoG controls membrane protrusion formation. Finally, silencing endothelial Trio expression or reducing TrioD1 activity without affecting SGEF impairs both docking structure formation and leukocyte transmigration. We conclude that Trio promotes leukocyte transendothelial migration by inducing endothelial docking structure formation in a filamin-dependent manner through the activation of Rac1 and RhoG.
- Published
- 2012
29. Two-fold emission from the S-shell of PbSe/CdSe core/shell quantum dots
- Author
-
Marijn A. van Huis, Dominika Grodzinska, Celso de Mello Donegá, Renee Dorland, Jos van Rijssel, Daniel Vanmaekelbergh, Andries Meijerink, and Wiel H. Evers
- Subjects
Materials science ,Photoluminescence ,Optical Phenomena ,Exciton ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,7. Clean energy ,Spectral line ,Absorption ,Biomaterials ,Core shell ,Microscopy, Electron, Transmission ,Quantum Dots ,Cadmium Compounds ,General Materials Science ,Selenium Compounds ,Thermal equilibrium ,Physics ,Spectrum Analysis ,Temperature ,General Chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter::Mesoscopic Systems and Quantum Hall Effect ,0104 chemical sciences ,Chemistry ,Lead ,Quantum dot ,Luminescent Measurements ,Nanoparticles ,Atomic physics ,0210 nano-technology ,Biotechnology - Abstract
The optical properties of PbSe/CdSe core/shell quantum dots with core sizes smaller than 4 nm in the 5300 K range are reported. The photoluminescence spectra show two peaks, which become increasingly separated in energy as the core diameter is reduced below 4 nm. It is shown that these peaks are due to intrinsic exciton transitions in each quantum dot, rather than emission from different quantum dot sub-ensembles. Most likely, the energy separation between the peaks is due to inter-valley coupling between the L-points of PbSe. The temperature dependence of the relative intensities of the peaks implies that the two emitting states are not in thermal equilibrium and that dark exciton states must play an important role.
- Published
- 2011
30. Inside-Out Regulation of ICAM-1 Dynamics in TNF-alpha-Activated Endothelium
- Author
-
Floris P. J. van Alphen, Jos van Rijssel, Simon Tol, Peter L. Hordijk, Jaap D. van Buul, Kees A. Hoeben, Mark Hoogenboezem, Jan van Marle, Erik Mul, Landsteiner Laboratory, Cell Biology and Histology, Physiology, and Faculteit der Geneeskunde
- Subjects
Science ,Blotting, Western ,Intercellular Adhesion Molecule-1 ,Filamin ,Cell Biology/Cell Signaling ,chemistry.chemical_compound ,Cell Biology/Cytoskeleton ,Cell Adhesion ,Humans ,Cell adhesion ,Cytoskeleton ,Cytochalasin B ,Cells, Cultured ,Microscopy, Confocal ,Multidisciplinary ,Tumor Necrosis Factor-alpha ,Chemistry ,Cell adhesion molecule ,Apical membrane ,Actin cytoskeleton ,Cell biology ,Cell Biology/Cell Adhesion ,Microscopy, Electron, Scanning ,Medicine ,Endothelium, Vascular ,Research Article - Abstract
BackgroundDuring transendothelial migration, leukocytes use adhesion molecules, such as ICAM-1, to adhere to the endothelium. ICAM-1 is a dynamic molecule that is localized in the apical membrane of the endothelium and clusters upon binding to leukocytes. However, not much is known about the regulation of ICAM-1 clustering and whether membrane dynamics are linked to the ability of ICAM-1 to cluster and bind leukocyte integrins. Therefore, we studied the dynamics of endothelial ICAM-1 under non-clustered and clustered conditions.Principal findingsDetailed scanning electron and fluorescent microscopy showed that the apical surface of endothelial cells constitutively forms small filopodia-like protrusions that are positive for ICAM-1 and freely move within the lateral plane of the membrane. Clustering of ICAM-1, using anti-ICAM-1 antibody-coated beads, efficiently and rapidly recruits ICAM-1. Using fluorescence recovery after photo-bleaching (FRAP), we found that clustering increased the immobile fraction of ICAM-1, compared to non-clustered ICAM-1. This shift required the intracellular portion of ICAM-1. Moreover, biochemical assays showed that ICAM-1 clustering recruited beta-actin and filamin. Cytochalasin B, which interferes with actin polymerization, delayed the clustering of ICAM-1. In addition, we could show that cytochalasin B decreased the immobile fraction of clustered ICAM-1-GFP, but had no effect on non-clustered ICAM-1. Also, the motor protein myosin-II is recruited to ICAM-1 adhesion sites and its inhibition increased the immobile fraction of both non-clustered and clustered ICAM-1. Finally, blocking Rac1 activation, the formation of lipid rafts, myosin-II activity or actin polymerization, but not Src, reduced the adhesive function of ICAM-1, tested under physiological flow conditions.ConclusionsTogether, these findings indicate that ICAM-1 clustering is regulated in an inside-out fashion through the actin cytoskeleton. Overall, these data indicate that signaling events within the endothelium are required for efficient ICAM-1-mediated leukocyte adhesion.
- Published
- 2010
31. Universal role of discrete acoustic phonons in the low-temperature optical emission of colloidal quantum dots
- Author
-
Dan Oron, Uri Banin, Andries Meijerink, Assaf Aharoni, Celso de Mello Donegá, Jos van Rijssel, Condensed Matter and Interfaces, Physical and Colloid Chemistry, Dep Scheikunde, and Sub Physical and Colloid Chemistry
- Subjects
Physics ,Condensed matter physics ,Phonon ,General Physics and Astronomy ,Heterojunction ,Condensed Matter::Mesoscopic Systems and Quantum Hall Effect ,symbols.namesake ,Coupling (physics) ,Pauli exclusion principle ,Quantum dot ,Crystal field theory ,Radiative transfer ,symbols ,Ground state - Abstract
Multiple energy scales contribute to the radiative properties of colloidal quantum dots, including magnetic interactions, crystal field splitting, Pauli exclusion, and phonons. Identification of the exact physical mechanism which couples first to the dark ground state of colloidal quantum dots, inducing a significant reduction in the radiative lifetime at low temperatures, has thus been under significant debate. Here we present measurements of this phenomenon on a variety of materials as well as on colloidal heterostructures. These show unambiguously that the dominant mechanism is coupling of the ground state to a confined acoustic phonon, and that this mechanism is universal.
- Published
- 2008
32. Exciton storage by Mn(2+) in colloidal Mn(2+)-doped CdSe quantum dots
- Author
-
Andries Meijerink, Paul I. Archer, Rémi Beaulac, Daniel R. Gamelin, and Jos van Rijssel
- Subjects
Photoluminescence ,Exciton ,Bioengineering ,02 engineering and technology ,010402 general chemistry ,7. Clean energy ,01 natural sciences ,Molecular physics ,Condensed Matter::Materials Science ,General Materials Science ,Biexciton ,Dopant ,Condensed matter physics ,Condensed Matter::Other ,Chemistry ,Mechanical Engineering ,Doping ,General Chemistry ,Condensed Matter::Mesoscopic Systems and Quantum Hall Effect ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,0104 chemical sciences ,Quantum dot ,Excited state ,0210 nano-technology ,Luminescence - Abstract
Colloidal Mn (2+)-doped CdSe quantum dots showing long excitonic photoluminescence decay times of up to tau exc = 15 mus at temperatures over 100 K are described. These decay times exceed those of undoped CdSe quantum dots by approximately 10 (3) and are shown to arise from the creation of excitons by back energy transfer from excited Mn (2+) dopant ions. A kinetic model describing thermal equilibrium between Mn (2+ 4)T 1 and CdSe excitonic excited states reproduces the experimental observations and reveals that, for some quantum dots, excitons can emit with near unity probability despite being approximately 100 meV above the Mn (2+ 4)T 1 state. The effect of Mn (2+) doping on CdSe quantum dot luminescence at high temperatures is thus completely opposite from that at low temperatures described previously.
- Published
- 2008
33. A local VE-cadherin and Trio-based signaling complex stabilizes endothelial junctions through Rac1
- Author
-
Ilse Timmerman, Jeffrey Kroon, Niels Heemskerk, Yi I. Wu, Jakobus van Unen, Jos van Rijssel, Antje Schaefer, Theodorus W. J. Gadella, Joachim Goedhart, Taofei Yin, Mark Hoogenboezem, Jaap D. van Buul, Stephan Huveneers, CCA - Immuno-pathogenesis, Faculteit der Geneeskunde, Molecular Cytology (SILS, FNWI), and Landsteiner Laboratory
- Subjects
rac1 GTP-Binding Protein ,Cell ,RAC1 ,Protein Serine-Threonine Kinases ,Biology ,Cell junction ,GTP Phosphohydrolases ,Capillary Permeability ,Adherens junction ,Endothelial barrier ,Antigens, CD ,Human Umbilical Vein Endothelial Cells ,medicine ,Guanine Nucleotide Exchange Factors ,Humans ,Cytoskeleton ,Molecular Biology ,Actin ,Cadherin ,Endothelial Cells ,Correction ,Cell Biology ,Cadherins ,Actin cytoskeleton ,Cell biology ,Actin Cytoskeleton ,Intercellular Junctions ,medicine.anatomical_structure ,Förster resonance energy transfer ,Endothelium, Vascular ,VE-cadherin ,Signal Transduction ,Developmental Biology - Abstract
Endothelial cell-cell junctions maintain a restrictive barrier that is tightly regulated to allow dynamic responses to permeability-inducing angiogenic factors, as well as to inflammatory agents and adherent leukocytes. The ability of these stimuli to transiently remodel adherens junctions depends on Rho-GTPase-controlled cytoskeletal rearrangements. How the activity of Rho-GTPases is spatio-temporally controlled at endothelial adherens junctions by guanine-nucleotide exchange factors (GEFs) is incompletely understood. Here, we identify a crucial role for the Rho-GEF Trio in stabilizing junctions based around vascular endothelial (VE)-cadherin (also known as CDH5). Trio interacts with VE-cadherin and locally activates Rac1 at adherens junctions during the formation of nascent contacts, as assessed using a novel FRET-based Rac1 biosensor and biochemical assays. The Rac-GEF domain of Trio is responsible for the remodeling of junctional actin from radial into cortical actin bundles, a crucial step for junction stabilization. This promotes the formation of linear adherens junctions and increases endothelial monolayer resistance. Collectively, our data show the importance of spatio-temporal regulation of the actin cytoskeleton through Trio and Rac1 at VE-cadherin-based cell-cell junctions in the maintenance of the endothelial barrier.
- Published
- 2015
34. Exciton Storage by Mn2+in Colloidal Mn2+-Doped CdSe Quantum Dots.
- Author
-
Rémi Beaulac, Paul I. Archer, Jos van Rijssel, Andries Meijerink, and Daniel R. Gamelin
- Published
- 2008
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