© Raphael Schleutker

Research Topic

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.

Selected Publications

  • De Vries, W.C.§, Kudruk, S.§, Grill, D., Niehues, M., Matos, A.L.L., Wissing, M., Studer, A.,Gerke, V.*, and Ravoo, B.J.* (2019). Controlled cellular delivery of amphiphilic cargo by redox-responsive nanocontainers. Adv Sci 6, 1901935. (§first authors, *corresponding authors).
  • Holthenrich, A., Drexler, H.C.A., Chehab, T., Naß, J., and Gerke, V. (2019). Proximity proteomics of endothelial Weibel-Palade bodies identifies novel regulator of von Willebrand factor secretion. Blood 134, 979-982.
  • Rakers, L.§, Grill, D. §, Matos, A.L.L., Wulff, S., Wang, D., Börgel, J., Körsgen, M., Arlinghaus, H.F., Galla, H.J.*, Gerke, V.*, and Glorius, F.* (2018). Addressable cholesterol analogs for live imaging of cellular membranes. Cell Chem Biol 25, 952-961. (§first authors, *corresponding authors).
  • 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)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.