Biological membranes are dynamic structures that can organize into a large number of transient domains of different sizes and stability. The formation and function of these membrane domains are determined by properties of the membrane lipids, those of integrated and associated membrane proteins as well as contacts to the underlying cytoskeleton. We study general aspects of cell membrane organization focusing on the biological role of membrane domains in intracellular trafficking. Central questions are: (i) What is the nature of transient membrane domains that serve as hubs for endo- and/or exocytosis at the plasma membrane, (ii) How do these membrane domains form and how are they stabilized, (iii) How does their dynamic nature affect membrane transport from and to the plasma membrane. Here we focus on two central membrane-related events in endothelial cells that form the inner lining of blood vessels. First, the regulated exocytosis of unique secretory granules, the Weibel-Palade bodies that store important factors controlling vascular hemostasis and local inflammation. Second, the rapid repair of plasma membrane wounds that are inflicted by mechanical stress, e.g. in the course of interactions with circulating leukocytes. We use live cell microscopy to visualize membrane domains and vesicle trafficking in primary endothelial cells and model membranes of defined composition to study biophysical and biochemical parameters of membranes.
- Boye TL, Maeda K, Pezeshkian W, Sønder SL, Haeger SC, Gerke V, Simonsen AC, Nylandsted J. (2017). Annexin A4 and A6 induce membrane curvature and constriction during cell membrane repair. Nat Commun 8:1623. doi: 10.1038/s41467-017-01743-6.
- Brandherm, I., Disse, J., Zeuschner, D. and Gerke, V. (2013). cAMP-induced secretion of endothelial von Willebrand factor is regulated by a phosphorylation/dephosphorylation switch in annexin A2. Blood 122, 1042-1051.
- Chehab, T.*, Criado Santos, N.*, Holthenrich, A., Koerdt, S.N., Disse, J., Schuberth, C., Nazmi, A.R., Neeft, M., Koch, H., Man, K.N.M., Wojcik, S.M., Martin, T.F.J., van der Sluijs, P., Brose, N. and Gerke, V. (2017). A novel Munc13-4/S100A10/Annexin A2 complex promotes Weibel-Palade body exocytosis in endothelial cells. Mol Biol Cell 28, 1688-1700.
- De Vries, W., Grill, D., Tesch, M., Ricker, A., Nüsse, H., Klingauf, J., Studer, A. *, Gerke, V. *, Ravoo, B.J. * (2017) Self-assembly of redox-responsive polymer nanocontainers for intracellular delivery by a reversible supramolecular stabilization of vesicles. Angew Chem Int Ed 56, 9603-9607. (*corresponding authors)
- Disse, J., Vitale, N., Bader, M.F. and Gerke, V. (2009). Phospholipase D1 is specifically required for the regulated secretion of von Willebrand factor from endothelial cells. Blood 113, 973-980.
- Drücker, P., Pejic, M., Grill, D., Galla, H.J. and Gerke, V. (2014). Cooperative binding of annexin A2 to cholesterol- and phosphatidylinositol-4,5-bisphosphate-containing bilayers. Biophys J 107, 2070-2081.
- Drücker, P., Pejic, M., Galla, H.J. and Gerke, V. (2013). Lipid segregation and membrane budding induced by the peripheral membrane binding protein annexin A2. J Biol Chem 288, 24764-24776.
- Gerke, V., Creutz, C.E. and Moss, S.E. (2005). Annexins: Linking Ca2+ signalling to membrane dynamics. Nat Rev Mol Cell Biol 6, 449-461.
- Koerdt, S.N. and Gerke, V. (2017). Annexin A2 is involved in Ca(2+)-dependent membrane repair in primary human endothelial cells. Biophys Biochim Acta Mol Cell Res 1864, 1046-1053.
- Poeter M, Brandherm I, Rossaint J, Rosso G, Shahin V, Skryabin BV, Zarbock A, Gerke V, Rescher U. (2014). Annexin A8 controls leukocyte recruitment to activated endothelial cells via cell surface delivery of CD63. Nat Commun 5:3738. doi: 10.1038/ncomms4738.
- Rojo Pulido, I., Nightingale, T.D., Darchen, F., Seabra, M.C., Cutler, D.F. and Gerke, V. (2011). Myosin Va acts in concert with Rab27a and MyRIP to regulate acute von-Willebrand factor release from endothelial cells. Traffic 12, 1371-1382.
- Pulido, I.R., Jahn, R. and Gerke, V. (2011). VAMP3 is associated with endothelial Weibel-Palade bodies and participates in their Ca(2+)-dependent exocytosis. Biophys Biochim Acta Mol Cell Res 1813, 1038-1044