Search

Your search keyword '"Bebelman, Maarten P."' showing total 21 results
Start Over Author "Bebelman, Maarten P." Search Limiters Available in Library Collection
21 results on '"Bebelman, Maarten P."'

3. Hypoxia and TNF‐alpha modulate extracellular vesicle release from human induced pluripotent stem cell‐derived cardiomyocytes.

Author

Viola, Margarida, Bebelman, Maarten P., Maas, Renee G. C., de Voogt, Willemijn S., Verweij, Frederik J., Seinen, Cor S., de Jager, Saskia C. A., Vader, Pieter, Pegtel, Dirk Michiel, and Petrus Gerardus Sluijter, Joost

Subjects
*EXTRACELLULAR vesicles, *HOMEOSTASIS, *MYOCARDIAL infarction, *CELL communication, *SMALL molecules, *PLURIPOTENT stem cells
Abstract

Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication in the heart under homeostatic and pathological conditions, such as myocardial infarction (MI). However, the basic mechanisms driving cardiomyocyte‐derived EV (CM‐EV) production following stress are poorly understood. In this study, we generated human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) that express NanoLuc‐tetraspanin reporters. These modified hiPSC‐CMs allow for quantification of tetraspanin‐positive CM‐EV secretion from small numbers of cells without the need for time‐consuming EV isolation techniques. We subjected these cells to a panel of small molecules to study their effect on CM‐EV biogenesis and secretion under basal and stress‐associated conditions. We observed that EV biogenesis is context‐dependent in hiPSC‐CMs. Nutrient starvation decreases CM‐EV secretion while hypoxia increases the production of CM‐EVs in a nSmase2‐dependent manner. Moreover, the inflammatory cytokine TNF‐α increased CM‐EV secretion through a process involving NLRP3 inflammasome activation and mTOR signalling. Here, we detailed for the first time the regulatory mechanisms of EV biogenesis in hiPSC‐CMs upon MI‐associated stressors. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

5. The human cytomegalovirus-encoded G protein–coupled receptor UL33 exhibits oncomodulatory properties

Author

van Senten, Jeffrey R., Bebelman, Maarten P., Fan, Tian Shu, Heukers, Raimond, Bergkamp, Nick D., van Gasselt, Puck, Langemeijer, Ellen V., Slinger, Erik, Lagerweij, Tonny, Rahbar, Afsar, Stigter-van Walsum, Marijke, Maussang, David, Leurs, Rob, Musters, René J.P., van Dongen, Guus A.M.S., Söderberg-Nauclér, Cecilia, Würdinger, Thomas, Siderius, Marco, and Smit, Martine J.

Published
2019
Full Text
View/download PDF

6. The constitutive activity of the virally encoded chemokine receptor US28 accelerates glioblastoma growth

Author

Heukers, Raimond, Fan, Tian Shu, de Wit, Raymond H., van Senten, Jeffrey R., De Groof, Timo W. M., Bebelman, Maarten P., Lagerweij, Tonny, Vieira, Joao, de Munnik, Sabrina M., Smits-de Vries, Laura, van Offenbeek, Jody, Rahbar, Afsar, van Hoorick, Diane, Söderberg-Naucler, Cecilia, Würdinger, Thomas, Leurs, Rob, Siderius, Marco, Vischer, Henry F., and Smit, Martine J.

Published
2018
Full Text
View/download PDF

7. Exosomal release of the virus-encoded chemokine receptor US28 contributes to chemokine scavenging

Author

Bebelman, Maarten P, Setiawan, Irfan M, Bergkamp, Nick D, van Senten, Jeffrey R, Crudden, Caitrin, Bebelman, Jan Paul M, Verweij, Frederik J, van Niel, Guillaume, Siderius, Marco, Pegtel, D Michiel, Smit, Martine J, Bebelman, Maarten P, Setiawan, Irfan M, Bergkamp, Nick D, van Senten, Jeffrey R, Crudden, Caitrin, Bebelman, Jan Paul M, Verweij, Frederik J, van Niel, Guillaume, Siderius, Marco, Pegtel, D Michiel, and Smit, Martine J

Abstract

The human cytomegalovirus (HCMV)-encoded chemokine receptor US28 contributes to various aspects of the viral life cycle and promotes immune evasion by scavenging chemokines from the microenvironment of HCMV-infected cells. In contrast to the plasma membrane localization of most human chemokine receptors, US28 has a predominant intracellular localization. In this study, we used immunofluorescence and electron microscopy to determine the localization of US28 upon exogenous expression, as well as in HCMV-infected cells. We observed that US28 localizes to late endosomal compartments called multivesicular bodies (MVBs), where it is sorted in intraluminal vesicles. Live-cell total internal reflection fluorescence (TIRF) microscopy revealed that US28-containing MVBs can fuse with the plasma membrane, resulting in the secretion of US28 on exosomes. Exosomal US28 binds the chemokines CX 3CL1 and CCL5, and US28-containing exosomes inhibited the CX 3CL1-CX 3CR1 signaling axis. These findings suggest that exosomal release of US28 contributes to chemokine scavenging and immune evasion by HCMV.

Published
2023

8. Exosomal release of the virus-encoded chemokine receptor US28 contributes to chemokine scavenging

Author

Sub Cell Biology, Cell Biology, Neurobiology and Biophysics, Bebelman, Maarten P, Setiawan, Irfan M, Bergkamp, Nick D, van Senten, Jeffrey R, Crudden, Caitrin, Bebelman, Jan Paul M, Verweij, Frederik J, van Niel, Guillaume, Siderius, Marco, Pegtel, D Michiel, Smit, Martine J, Sub Cell Biology, Cell Biology, Neurobiology and Biophysics, Bebelman, Maarten P, Setiawan, Irfan M, Bergkamp, Nick D, van Senten, Jeffrey R, Crudden, Caitrin, Bebelman, Jan Paul M, Verweij, Frederik J, van Niel, Guillaume, Siderius, Marco, Pegtel, D Michiel, and Smit, Martine J

Published
2023

9. A virally encoded GPCR drives glioblastoma through feed-forward activation of the SK1-S1P1 signaling axis

Author

Bergkamp, Nick D., van Senten, Jeffrey R., Brink, Hendrik J., Bebelman, Maarten P., van den Bor, Jelle, Çobanoğlu, Tuğçe S., Dinkla, Kasper, Köster, Johannes, Klau, Gunnar, Siderius, Marco, Smit, Martine J., Bergkamp, Nick D., van Senten, Jeffrey R., Brink, Hendrik J., Bebelman, Maarten P., van den Bor, Jelle, Çobanoğlu, Tuğçe S., Dinkla, Kasper, Köster, Johannes, Klau, Gunnar, Siderius, Marco, and Smit, Martine J.

Abstract

The G protein-coupled receptor (GPCR) US28 encoded by the human cytomegalovirus (HCMV) is associated with accelerated progression of glioblastomas, aggressive brain tumors with a generally poor prognosis. Here, we showed that US28 increased the malignancy of U251 glioblastoma cells by enhancing signaling mediated by sphingosine-1-phosphate (S1P), a bioactive lipid that stimulates oncogenic pathways in glioblastoma. US28 expression increased the abundance of the key components of the S1P signaling axis, including an enzyme that generates S1P [sphingosine kinase 1 (SK1)], an S1P receptor [S1P receptor 1 (S1P1)], and S1P itself. Enhanced S1P signaling promoted glioblastoma cell proliferation and survival by activating the kinases AKT and CHK1 and the transcriptional regulators cMYC and STAT3 and by increasing the abundance of cancerous inhibitor of PP2A (CIP2A), driving several feed-forward signaling loops. Inhibition of S1P signaling abrogated the proliferative and anti-apoptotic effects of US28. US28 also activated the S1P signaling axis in HCMV-infected cells. This study uncovers central roles for S1P and CIP2A in feed-forward signaling that contributes to the US28-mediated exacerbation of glioblastoma.

Published
2023
Full Text
View/download PDF

12. ER Membrane Contact Sites support endosomal small GTPase conversion for exosome secretion

Author

Verweij, Frederik, Bebelman, Maarten P, George, Anna, Couty, Mickael, Bécot, Anaïs, Palmulli, Roberta, Heiligenstein, Xavier, Sires-Campos, Julia, Raposo, Graca, Pegtel, Dirk Michiel, Van Niel, Guillaume, Verweij, Frederik, Bebelman, Maarten P, George, Anna, Couty, Mickael, Bécot, Anaïs, Palmulli, Roberta, Heiligenstein, Xavier, Sires-Campos, Julia, Raposo, Graca, Pegtel, Dirk Michiel, and Van Niel, Guillaume

Abstract

Exosomes are endosome-derived extracellular vesicles involved in intercellular communication. They are generated as intraluminal vesicles within endosomal compartments that fuse with the plasma membrane (PM). The molecular events that generate secretory endosomes and lead to the release of exosomes are not well understood. We identified a subclass of non-proteolytic endosomes at prelysosomal stage as the compartment of origin of CD63 positive exosomes. These compartments undergo a Rab7a/Arl8b/Rab27a GTPase cascade to fuse with the PM. Dynamic endoplasmic reticulum (ER)-late endosome (LE) membrane contact sites (MCS) through ORP1L have the distinct capacity to modulate this process by affecting LE motility, maturation state, and small GTPase association. Thus, exosome secretion is a multi-step process regulated by GTPase switching and MCS, highlighting the ER as a new player in exosome-mediated intercellular communication.

Published
2022

13. ER Membrane Contact Sites support endosomal small GTPase conversion for exosome secretion

Author

Sub Cell Biology, Celbiologie, Verweij, Frederik, Bebelman, Maarten P, George, Anna, Couty, Mickael, Bécot, Anaïs, Palmulli, Roberta, Heiligenstein, Xavier, Sires-Campos, Julia, Raposo, Graca, Pegtel, Dirk Michiel, Van Niel, Guillaume, Sub Cell Biology, Celbiologie, Verweij, Frederik, Bebelman, Maarten P, George, Anna, Couty, Mickael, Bécot, Anaïs, Palmulli, Roberta, Heiligenstein, Xavier, Sires-Campos, Julia, Raposo, Graca, Pegtel, Dirk Michiel, and Van Niel, Guillaume

Published
2022

16. The Convergence of Extracellular Vesicle and GPCR Biology

Author

Bebelman, Maarten P., Crudden, Caitrin, Pegtel, D. Michiel, Smit, Martine J., Bebelman, Maarten P., Crudden, Caitrin, Pegtel, D. Michiel, and Smit, Martine J.

Abstract

Transmembrane receptors, of which G protein-coupled receptors (GPCRs) constitute the largest group, typically act as cellular antennae that reside at the plasma membrane (PM) to collect and interpret information from the extracellular environment. The discovery of cell-released extracellular vesicles (EVs) has added a new dimension to intercellular communication. These unique nanocarriers reflect cellular topology and can systemically transport functionally competent transmembrane receptors, ligands, and a cargo of signal proteins. Recent developments hint at roles for GPCRs in the EV life cycle and, conversely, at roles for EVs in GPCR signal transduction. We highlight key points of convergence, discuss their relevance to current GPCR and EV paradigms, and speculate on how this intersection could lend itself to future therapeutic avenues.

Published
2020
Full Text
View/download PDF

17. Quantifying exosome secretion from single cells reveals a modulatory role for GPCR signaling

Author

Verweij, Frederik Johannes, Bebelman, Maarten P., Jimenez, Connie R., Garcia-Vallejo, Juan J., Janssen, Hans, Neefjes, Jacques, Knol, Jaco C., de Goeij-de Haas, Richard, Piersma, Sander R., Baglio, S. Rubina, Verhage, Matthijs, Middeldorp, Jaap M., Zomer, Anoek, van Rheenen, Jacco, Coppolino, Marc G., Hurbain, Ilse, Raposo, Graça, Smit, Martine J., Toonen, Ruud F.G., van Niel, Guillaume, Pegtel, D. Michiel, Verweij, Frederik Johannes, Bebelman, Maarten P., Jimenez, Connie R., Garcia-Vallejo, Juan J., Janssen, Hans, Neefjes, Jacques, Knol, Jaco C., de Goeij-de Haas, Richard, Piersma, Sander R., Baglio, S. Rubina, Verhage, Matthijs, Middeldorp, Jaap M., Zomer, Anoek, van Rheenen, Jacco, Coppolino, Marc G., Hurbain, Ilse, Raposo, Graça, Smit, Martine J., Toonen, Ruud F.G., van Niel, Guillaume, and Pegtel, D. Michiel

Published
2018

18. Correction: Quantifying exosome secretion from single cells reveals a modulatory role for GPCR signaling

Author

Verweij, Frederik Johannes, Bebelman, Maarten P, Jimenez, Connie R, Garcia-Vallejo, Juan J, Janssen, Hans, Neefjes, Jacques, Knol, Jaco C, de Goeij-de Haas, Richard, Piersma, Sander R, Baglio, S Rubina, Verhage, Matthijs, Middeldorp, Jaap M, Zomer, Anoek, van Rheenen, Jacco, Coppolino, Marc G, Hurbain, Ilse, Raposo, Graça, Smit, Martine J, Toonen, Ruud F G, van Niel, Guillaume, Pegtel, D Michiel, Verweij, Frederik Johannes, Bebelman, Maarten P, Jimenez, Connie R, Garcia-Vallejo, Juan J, Janssen, Hans, Neefjes, Jacques, Knol, Jaco C, de Goeij-de Haas, Richard, Piersma, Sander R, Baglio, S Rubina, Verhage, Matthijs, Middeldorp, Jaap M, Zomer, Anoek, van Rheenen, Jacco, Coppolino, Marc G, Hurbain, Ilse, Raposo, Graça, Smit, Martine J, Toonen, Ruud F G, van Niel, Guillaume, and Pegtel, D Michiel

Published
2018
Full Text
View/download PDF

19. Quantifying exosome secretion from single cells reveals a modulatory role for GPCR signaling

Author

CMM Sectie Molecular Cancer Research, Cancer, Verweij, Frederik Johannes, Bebelman, Maarten P., Jimenez, Connie R., Garcia-Vallejo, Juan J., Janssen, Hans, Neefjes, Jacques, Knol, Jaco C., de Goeij-de Haas, Richard, Piersma, Sander R., Baglio, S. Rubina, Verhage, Matthijs, Middeldorp, Jaap M., Zomer, Anoek, van Rheenen, Jacco, Coppolino, Marc G., Hurbain, Ilse, Raposo, Graça, Smit, Martine J., Toonen, Ruud F.G., van Niel, Guillaume, Pegtel, D. Michiel, CMM Sectie Molecular Cancer Research, Cancer, Verweij, Frederik Johannes, Bebelman, Maarten P., Jimenez, Connie R., Garcia-Vallejo, Juan J., Janssen, Hans, Neefjes, Jacques, Knol, Jaco C., de Goeij-de Haas, Richard, Piersma, Sander R., Baglio, S. Rubina, Verhage, Matthijs, Middeldorp, Jaap M., Zomer, Anoek, van Rheenen, Jacco, Coppolino, Marc G., Hurbain, Ilse, Raposo, Graça, Smit, Martine J., Toonen, Ruud F.G., van Niel, Guillaume, and Pegtel, D. Michiel

Published
2018

20. Correction: Quantifying exosome secretion from single cells reveals a modulatory role for GPCR signaling

Author

Verweij, Frederik Johannes, primary, Bebelman, Maarten P., additional, Jimenez, Connie R., additional, Garcia-Vallejo, Juan J., additional, Janssen, Hans, additional, Neefjes, Jacques, additional, Knol, Jaco C., additional, de Goeij-de Haas, Richard, additional, Piersma, Sander R., additional, Baglio, S. Rubina, additional, Verhage, Matthijs, additional, Middeldorp, Jaap M., additional, Zomer, Anoek, additional, van Rheenen, Jacco, additional, Coppolino, Marc G., additional, Hurbain, Ilse, additional, Raposo, Graça, additional, Smit, Martine J., additional, Toonen, Ruud F.G., additional, van Niel, Guillaume, additional, and Pegtel, D. Michiel, additional

Published
2018
Full Text
View/download PDF

21. Quantifying exosome secretion from single cells reveals a modulatory role for GPCR signaling

Author

Verweij, Frederik Johannes, primary, Bebelman, Maarten P., additional, Jimenez, Connie R., additional, Garcia-Vallejo, Juan J., additional, Janssen, Hans, additional, Neefjes, Jacques, additional, Knol, Jaco C., additional, de Goeij-de Haas, Richard, additional, Piersma, Sander R., additional, Baglio, S. Rubina, additional, Verhage, Matthijs, additional, Middeldorp, Jaap M., additional, Zomer, Anoek, additional, van Rheenen, Jacco, additional, Coppolino, Marc G., additional, Hurbain, Ilse, additional, Raposo, Graça, additional, Smit, Martine J., additional, Toonen, Ruud F.G., additional, van Niel, Guillaume, additional, and Pegtel, D. Michiel, additional

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results