Subproject A01: Generation of specificity in post-Golgi trafficking
Principal investigator:
Prof. Dr. Gerd Jürgens
Universität Tübingen
ZMBP, Entwicklungsgenetik
Auf der Morgenstelle 3, 72076 Tübingen
Tel 07071 – 29 78886
Fax 07071 – 29 5797
gerd.juergens@zmbp.uni-tuebingen.de
Summary:
Membrane traffic maintains the functional organisation of the eukaryotic cell and mediates the exchange of information between neighbouring cells as well as physiological responses to external signals. Post-Golgi traffic occurs between endosomal compartments and the plasma membrane including secretion, endocytosis, recycling and vacuolar traffic. How specificity is generated in post-Golgi trafficking is essentially unknown. Our project is to address the roles of guanine-nucleotide exchange factors of ARF GTPases (ARF-GEFs), focussing on how their membrane association and interaction with ARF substrates and coat proteins might regulate specific post-Golgi trafficking pathways. Results obtained so far suggest different ARF-GEFs activate the same ARF class, resulting in membrane recruitment of pathway-specific coat proteins. To elucidate molecular mechanisms of membrane-specific action of related ARF-GEFs, we will determine the structure of recycling ARF-GEF GNOM in comparison to its non-recycling paralogue GNL1, analyse how the formation of GNOM-GNL1 heterodimers is prevented and investigate what molecular features of ARF-GEFs are required for association with endosomal membranes. Finally, we will address mechanisms of pathway-specific membrane recruitment of different coat proteins mediating selective cargo transport.