Bestimmung der molekularen Mechanismen extrazellulärer Vesikelbildung
Entwicklungsbiologie
Zusammenfassung der Projektergebnisse
The main goal of this work was to better define the molecular mechanisms of extracellular vesicle (EV) budding from the plasma membrane, building from our previous finding that the lipid flippase TAT-5 inhibits EV release in C. elegans embryos (Wehman et al. 2011). We identified new proteins that regulate EV release and TAT-5 localization, as well as characterized new alleles of TAT-5 and cofactors that will allow us to perform unbiased screens in the future to identify additional molecules regulating EV release. We established that PAD-1 and MON-2 regulate TAT-5 localization, but that PAD-1 also regulates TAT-5 flippase activity to prevent ESCRT-mediated vesicle budding. We also determined how TAT-5 localization is regulated by sorting nexins in PI3P- and RME-8-dependent retromerindependent recycling pathways. We published five primary research articles, two review articles, and presented six posters and eight talks at international conferences based on this work.
Projektbezogene Publikationen (Auswahl)
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Extracellular vesicle budding is inhibited by redundant regulators of TAT-5 flippase localization and phospholipid asymmetry. Proceedings of the National Academy of Sciences, 115(6).
Beer, Katharina B.; Rivas-Castillo, Jennifer; Kuhn, Kenneth; Fazeli, Gholamreza; Karmann, Birgit; Nance, Jeremy F.; Stigloher, Christian & Wehman, Ann M.
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Biological membranes in EV biogenesis, stability, uptake, and cargo transfer: an ISEV position paper arising from the ISEV membranes and EVs workshop. Journal of Extracellular Vesicles, 8(1).
Russell, Ashley E.; Sneider, Alexandra; Witwer, Kenneth W.; Bergese, Paolo; Bhattacharyya, Suvendra N.; Cocks, Alexander; Cocucci, Emanuele; Erdbrügger, Uta; Falcon‐Perez, Juan M.; Freeman, David W.; Gallagher, Thomas M.; Hu, Shuaishuai; Huang, Yiyao; Jay, Steven M.; Kano, Shin‐ichi; Lavieu, Gregory; Leszczynska, Aleksandra; Llorente, Alicia M.; Lu, Quan ... & Vader, Pieter
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Degron-tagged reporters probe membrane topology and enable the specific labelling of membrane-wrapped structures. Nature Communications, 10(1).
Beer, Katharina B.; Fazeli, Gholamreza; Judasova, Kristyna; Irmisch, Linda; Causemann, Jona; Mansfeld, Jörg & Wehman, Ann M.
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Identification and characterization of TAT-5 interactors that regulate extracellular vesicle budding. PhD Doctoral thesis, University of Würzburg.
Beer, K.B.
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Loss of the Major Phosphatidylserine or Phosphatidylethanolamine Flippases Differentially Affect Phagocytosis. Frontiers in Cell and Developmental Biology, 8.
Fazeli, Gholamreza; Beer, Katharina B.; Geisenhof, Michaela; Tröger, Sarah; König, Julia; Müller-Reichert, Thomas & Wehman, Ann M.
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Conserved N- and C-terminal motifs of PAD-1 are required to inhibit extracellular vesicle release. MicroPubl Biol.
Pitts, L.R., Nguyen, A.T. & Wehman, Ann M.
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Dopey proteins are essential but overlooked regulators of membrane trafficking. Journal of Cell Science, 135(7).
Molière, Adrian; Beer, Katharina B. & Wehman, Ann M.
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Mechanism of lipid damage and their consequence for membrane stability. PhD thesis, University of Sao Paolo.
Inague, A.
