7 results on '"Sabine Kaltenbrunner"'
Search Results
2. Kinetoplastid‐specific <scp>X2</scp> ‐family kinesins interact with a kinesin‐like pleckstrin homology domain protein that localizes to the trypanosomal microtubule quartet
- Author
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Corinna Benz, Nora Müller, Sabine Kaltenbrunner, Hana Váchová, Marie Vancová, Julius Lukeš, Vladimír Varga, and Hassan Hashimi
- Subjects
Trypanosoma brucei brucei ,Protozoan Proteins ,Kinesins ,Pleckstrin Homology Domains ,Microtubules ,Molecular Biology ,Microbiology ,Cytoskeleton - Abstract
Kinesins are motor proteins found in all eukaryotic lineages that move along microtubules to mediate cellular processes such as mitosis and intracellular transport. In trypanosomatids, the kinesin superfamily has undergone a prominent expansion, resulting in one of the most diverse kinesin repertoires that includes the two kinetoplastid-restricted families X1 and X2. Here, we characterize in Trypanosoma brucei TbKifX2A, an orphaned X2 kinesin. TbKifX2A tightly interacts with TbPH1, a kinesin-like protein with a likely inactive motor domain, a rarely reported occurrence. Both TbKifX2A and TbPH1 localize to the microtubule quartet (MtQ), a characteristic but poorly understood cytoskeletal structure that wraps around the flagellar pocket as it extends to the cell body anterior. The proximal proteome of TbPH1 revealed two other interacting proteins, the flagellar pocket protein FP45 and intriguingly another X2 kinesin, TbKifX2C. Simultaneous ablation of TbKifX2A/TbPH1 results in the depletion of FP45 and TbKifX2C and also an expansion of the flagellar pocket, among other morphological defects. TbKifX2A is the first motor protein to be localized to the MtQ. The observation that TbKifX2C also associates with the MtQ suggests that the X2 kinesin family may have co-evolved with the MtQ, both kinetoplastid-specific traits.
- Published
- 2022
3. Kinetoplastid-specific X2-family kinesins interact with a kinesin-like pleckstrin homology domain protein that localizes to the trypanosomal microtubule quartet
- Author
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Vladimir Varga, Julius Lukeš, Sabine Kaltenbrunner, Hana Váchová, Marie Vancová, Hassan Hashimi, Corinna Benz, and Nora Müller
- Subjects
Pleckstrin homology domain ,Motor protein ,Microtubule ,parasitic diseases ,Basal body ,Kinesin ,Flagellum ,Biology ,Cytoskeleton ,Mitosis ,Cell biology - Abstract
Kinesins are motor proteins found in all eukaryotic lineages that move along microtubule tracks to mediate numerous cellular processes such as mitosis and intracellular transport of cargo. In trypanosomatids, the kinesin protein superfamily has undergone a prominent expansion, giving these protists one of the most diverse kinesin repertoires. This has led to the emergence of two trypanosomatid-restricted groups of kinesins. Here, we characterize in Trypanosoma brucei TbKifX2, a hitherto orphaned kinesin that belongs to one of these groups. Representing a rare instance, TbKifX2 tightly interacts with TbPH1, a kinesin-like protein with an inactive motor domain. TbPH1 is named after a pleckstrin homology (PH) domain present within its carboxy-terminal tail. TbKifX2 recruits TbPH1 to the microtubule quartet (MtQ), a characteristic but poorly understood cytoskeletal structure that is part of the multipartite flagellum attachment zone (FAZ) and extends from the basal body to the anterior of the cell body. The proximal proteome of TbPH1 is comprised of four proteins that localize to the FAZ, consistent with the notion that the TbKifX2/TbPH1 complex are the first identified proteins to bind the MtQ along its whole length. Simultaneous ablation of both TbKifX2 and TbPH1 leads to the formation of prominent protrusions from the cell posterior. Thus, these two trypanosomatid-restricted proteins, which specifically localize to the MtQ in a microtubule-rich cell, appear to be contributors to morphogenesis in T. brucei.
- Published
- 2021
4. Humoral and cellular immune responses in SARS-CoV-2 mRNA-vaccinated patients with cancer
- Author
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Mario Mairhofer, Susanne Kimeswenger, Riad Ghanem, Maria Pammer, Lea Kausche, Anna Habringer, Helmut J F Salzer, Soyoung Lee, Isabella Rauscher, Clemens A. Schmitt, Sabine Kaltenbrunner, Bernd Lamprecht, Christian Paar, Wolfram Hoetzenecker, Stefan Doppler, Maike Stegemann, and Katharina Klein
- Subjects
Cancer Research ,Messenger RNA ,2019-20 coronavirus outbreak ,Immunity, Cellular ,COVID-19 Vaccines ,Letter ,Coronavirus disease 2019 (COVID-19) ,business.industry ,SARS-CoV-2 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunity ,Cancer ,RNA ,COVID-19 ,medicine.disease ,Virology ,Immune system ,Oncology ,Neoplasms ,medicine ,Humans ,Public Health Surveillance ,RNA, Messenger ,business - Abstract
SARS-CoV-2 vaccines are effective in preventing COVID-19. Patients with cancer are at high risk for severe COVID-19 and are appropriately prioritized for vaccination. Several studies in this issue of Cancer Cell add to our knowledge of the heterogeneity of immune responses to vaccination among patients with cancer and identify important areas for future research.
- Published
- 2021
5. Virus-induced senescence is a driver and therapeutic target in COVID-19
- Author
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Markus Landthaler, Bernd Lamprecht, Riad Ghanem, Amjad Khan, Michael Mülleder, Maurice Reimann, Herta Steinkellner, Soyoung Lee, Emanuel Wyler, Mario Mairhofer, Wolfram Hoetzenecker, Paulina Richter-Pechanska, Séverine Kunz, Josef Tomasits, Rupert Langer, Kristina Dietert, Michael Schotsaert, Maria Pammer, Carles Martínez-Romero, Susanne Kimeswenger, Theresa C. Firsching, Jakob Trimpert, Melissa Uccellini, Achim D. Gruber, Bettina Purfürst, Adolfo García-Sastre, Clemens A. Schmitt, Reinhard Motz, Nikolaus Osterrieder, Anna Habringer, Markus Ralser, Julia Adler, Fahad Benthani, Martin Schönlein, Andrea Lau, Daniela Niemeyer, Christian Drosten, Dimitri Belenki, Dorothy N. Y. Fan, Roland Eils, Francesco Di Pierro, Lea Kausche, Gagandeep Singh, Christian Paar, Edward Georg Michaelis, Helmut J. F. Salzer, Yong Yu, and Sabine Kaltenbrunner
- Subjects
Senescence ,Male ,medicine.medical_treatment ,Dasatinib ,Inflammation ,Biology ,Cell Line ,Mice ,Immune system ,Cricetinae ,medicine ,Macrophage ,Animals ,Humans ,Molecular Targeted Therapy ,Senolytic ,Cellular Senescence ,Sulfonamides ,Multidisciplinary ,Aniline Compounds ,SARS-CoV-2 ,fungi ,COVID-19 ,Thrombosis ,Neutrophil extracellular traps ,COVID-19 Drug Treatment ,Disease Models, Animal ,Cytokine ,Apoptosis ,Cancer research ,Female ,Quercetin ,medicine.symptom - Abstract
Derailed cytokine and immune cell networks account for the organ damage and the clinical severity of COVID-19 (refs. 1–4). Here we show that SARS-CoV-2, like other viruses, evokes cellular senescence as a primary stress response in infected cells. Virus-induced senescence (VIS) is indistinguishable from other forms of cellular senescence and is accompanied by a senescence-associated secretory phenotype (SASP), which comprises pro-inflammatory cytokines, extracellular-matrix-active factors and pro-coagulatory mediators5–7. Patients with COVID-19 displayed markers of senescence in their airway mucosa in situ and increased serum levels of SASP factors. In vitro assays demonstrated macrophage activation with SASP-reminiscent secretion, complement lysis and SASP-amplifying secondary senescence of endothelial cells, which mirrored hallmark features of COVID-19 such as macrophage and neutrophil infiltration, endothelial damage and widespread thrombosis in affected lung tissue1,8,9. Moreover, supernatant from VIS cells, including SARS-CoV-2-induced senescence, induced neutrophil extracellular trap formation and activation of platelets and the clotting cascade. Senolytics such as navitoclax and a combination of dasatinib plus quercetin selectively eliminated VIS cells, mitigated COVID-19-reminiscent lung disease and reduced inflammation in SARS-CoV-2-infected hamsters and mice. Our findings mark VIS as a pathogenic trigger of COVID-19-related cytokine escalation and organ damage, and suggest that senolytic targeting of virus-infected cells is a treatment option against SARS-CoV-2 and perhaps other viral infections. Virus-induced senescence is a central pathogenic feature in COVID-19, and senolytics, which promote apoptosis of senescent cells, can reduce disease severity in hamsters,mice, as well as humans infected with SARS-CoV-2.
- Published
- 2021
6. Trypanosome Mitochondrial Translation and Tetracycline: No Sweat about Tet
- Author
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Sabine Kaltenbrunner, Hassan Hashimi, Alena Zíková, and Julius Lukeš
- Subjects
0301 basic medicine ,Mitochondrial translation ,Gene Expression ,Mitochondrion ,Ribosome ,Biochemistry ,Pearls ,SWEAT ,Antibiotics ,Protein biosynthesis ,Medicine and Health Sciences ,lcsh:QH301-705.5 ,Energy-Producing Organelles ,Protozoans ,biology ,Antimicrobials ,Drugs ,Drug Resistance, Microbial ,Anti-Bacterial Agents ,Mitochondria ,Nucleic acids ,Ribosomal RNA ,Tetracyclines ,Cellular Structures and Organelles ,medicine.drug ,lcsh:Immunologic diseases. Allergy ,Trypanosoma ,Tetracycline ,Immunology ,Bioenergetics ,Microbiology ,03 medical and health sciences ,Virology ,Microbial Control ,medicine ,Genetics ,Non-coding RNA ,Molecular Biology ,Pharmacology ,030102 biochemistry & molecular biology ,Organisms ,Biology and Life Sciences ,Cell Biology ,biology.organism_classification ,Molecular biology ,Parasitic Protozoans ,030104 developmental biology ,lcsh:Biology (General) ,Protein Biosynthesis ,RNA ,Parasitology ,Protein Translation ,lcsh:RC581-607 ,Ribosomes ,Trypanosoma Brucei Gambiense - Published
- 2016
7. Dynamics of Mitochondrial RNA-Binding Protein Complex in Trypanosoma brucei and Its Petite Mutant under Optimized Immobilization Conditions
- Author
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Eva Šimková, Sabine Kaltenbrunner, Julius Lukeš, Zhenqiu Huang, David Stanĕk, and Hassan Hashimi
- Subjects
Yellow fluorescent protein ,Cell Survival ,RNA, Mitochondrial ,Saccharomyces cerevisiae ,Trypanosoma brucei brucei ,Protozoan Proteins ,RNA-binding protein ,Trypanosoma brucei ,Mitochondrion ,Microbiology ,Mitochondrial Proteins ,parasitic diseases ,Molecular Biology ,biology ,RNA ,Fluorescence recovery after photobleaching ,RNA-Binding Proteins ,General Medicine ,Articles ,biology.organism_classification ,Cell biology ,Mutation ,Nucleic acid ,biology.protein ,RNA Interference - Abstract
There are a variety of complex metabolic processes ongoing simultaneously in the single, large mitochondrion of Trypanosoma brucei . Understanding the organellar environment and dynamics of mitochondrial proteins requires quantitative measurement in vivo . In this study, we have validated a method for immobilizing both procyclic stage (PS) and bloodstream stage (BS) T. brucei brucei with a high level of cell viability over several hours and verified its suitability for undertaking fluorescence recovery after photobleaching (FRAP), with mitochondrion-targeted yellow fluorescent protein (YFP). Next, we used this method for comparative analysis of the translational diffusion of mitochondrial RNA-binding protein 1 (MRP1) in the BS and in T. b. evansi . The latter flagellate is like petite mutant Saccharomyces cerevisiae because it lacks organelle-encoded nucleic acids. FRAP measurement of YFP-tagged MRP1 in both cell lines illuminated from a new perspective how the absence or presence of RNA affects proteins involved in mitochondrial RNA metabolism. This work represents the first attempt to examine this process in live trypanosomes.
- Published
- 2014
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