Project Details
Projekt
Role of deubiquitinating enzymes (DUBs) in Protein trafficking
Applicant
Professor Dr. Ralf Kölling
Subject Area
Cell Biology
Term
from 2008 to 2013
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 71267618
The fate of internalized cell surface proteins in eukaryotic cells is determined by their degree of ubiquitination. The mechanisms underlying ubiquitination-dependent sorting in the endocytic pathway will be examined more closely using the yeast ABC-transporter Ste6 as a model protein. At the level of early endosomes, ubiquitinated Ste6 is sorted into the lysosomal/vacuolar pathway for degradation, while non-ubiquitinated Ste6 is recycled back to the cell surface. In previous experiments, we found that recycling of non-ubiquitinated Ste6 is dependent on sorting nexin (Snx) 4 and on the monomeric clathrin adaptor Gga2. Our goal will be to examine how sorting nexins, clathrin adaptors and clathrin cooperate in ubiquitination-dependent sorting of Ste6. We will define recycling signals in Ste6 and look for proteins interacting with these signals. Of course, sorting nexins and clathrin adaptors are prime candidates for this analysis. The role of sorting nexins in tubular-based endosomal sorting is now becoming increasingly clear. At present, however, it is unclear how many distinct sorting pathways operate at the level of early endosomes and how cargo is specifically recognized. We established a working model that integrates most of the known data about the sorting of Ste6 and other yeast membrane proteins. This model will be tested by different experiments.
DFG Programme
Priority Programmes
