Molecular machinery mediating FGF2 membrane translocation in unconventional secretion (05)

• Subject Area: Cell Biology
• Term: from 2010 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 112927078

Fibroblast Growth Factor 2 (FGF2) is a tumor cell survival factor that is secreted via direct translocation across plasma membranes. The core mechanism of this unconventional secretory pathway is based upon PI(4,5)P2 dependent oligomerization and membrane insertion concomitant with the formation of a lipidic membrane pore. This project aims at (i) analyzing PI(4,5)P2 induced oligomerization by atomistic molecular dynamics simulations, (ii) studying the architecture of membrane inserted FGF2 oligomers by correlative light and cryo-electron microscopy and (iii) investigating the role of auxiliary factors in FGF2 membrane translocation using a fully reconstituted system with purified components.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 83: Molecular Architecture and Cellular Functions of Lipid/Protein Assemblies
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Project Head: Professor Dr. Walter Nickel