Groupleader: Walter Nickel

Our lab investigates unconventional mechanisms of protein secretion from mammalian cells. Our primary model cargo protein is fibroblast growth factor 2 (FGF2), a potent mitogen involved in tumor-induced angiogenesis.  As illustrated below, unconventional secretion of FGF2 occurs by direct translocation across plasma membranes (type I unconventional secretion), a process that involves sequential interactions with the phosphoinositide PI(4,5)P2 at the inner leaflet and heparan sulfate proteoglycans at the outer leaflet of plasma membranes.  FGF2 secretion from cells further depends on FGF2 being properly folded during all stages of membrane translocation.  Finally, tyrosine phosphorylation of FGF2 was found to be essential for the overall process of FGF2 secretion. Current research goals in the lab include the analysis of the molecular mechanism by which tyrosine phosphorylation affects FGF2 secretion. Furthermore, a major goal is to understand how FGF2 physically traverses the plasma membrane, a process that may involve FGF2 oligomerization and formation of a toroidal pore. These studies are likely to be relevant for other type I unconventional secretory proteins such as HIV Tat and Annexin A2.  Finally, the molecular mechanism of FGF2 secretion is used in the lab to develop inhibitors of this process that may lead to the development of a novel class of anti-angiogenic drugs for cancer therapy.



For further reading please download the review articles (download pdf) below.

Nickel and Rabouille, 2009.pdf
Nickel 2010 Curr Opin Biotechnolog.pdf
Nickel 2011 Traffic.pdf

Download BZH Report Nickel 2008-2010