Raft based sorting and domain-induced budding of post-Golgi transport carriers

• Applicant: Professor Dr. Kai Simons
• Subject Area: Virology
• Term: from 2005 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 13122793

Polarized cells establish and maintain functionally distinct surface domains by an elaborate sorting, which ensures accurate delivery of biosynthetic cargo to different parts of the plasma membrane. This is particularly evident in polarized epithelial cells such as the MDCK cell lines, which have been used as model systems for studies of sorting mechanisms. We postulate that the clustering of sphingolipid-cholesterol rafts through the oligomerization of raft components is used for segregating apical from basolateral cargo and generation of intracellular transport carriers. We have identified several new players in this process including lectins and phosphoinositide 4-phosphate-binding proteins. We will now use several approaches to analyze whether our working model for the formation of apical carriers is correct or not. One important element is that apical sorting is postulated to be driven by oligomerization of apical cargo proteins. This model will be tested by an experiment system developed by Crabtree and Schreiber based on regulated homodimerization.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1175: Dynamics of Cellular Membranes and their Exploitation by Viruses