Research Seminar: Coated vesicles (and what happens next...)
24 October 2018
Professor Margaret S. Robinson, FRS
Cambridge Institute for Medical Research, University of Cambridge
Tuesday 30th October, 1.00 p.m., Stacey Lecture Theatre 1
Coated vesicles package cargo proteins for transport between the membrane compartments of the cell. The coats on clathrin-coated vesicles (CCVs) consist mainly of clathrin and adaptor protein (AP) complexes, with AP-1 acting at intracellular membranes and AP-2 at the plasma membrane. Unlike the AP-2 pathway, the AP-1 pathway is not well understood. Moreover, there are additional clathrin-independent AP complexes. The talk will focus on AP-1 and AP-4. To understand the AP-1 pathway, we have used a combined approach including a method we developed called "knocksideways", which depletes AP-1 very rapidly, and a forward genetic screen for additional players, which identified a novel complex that appears to facilitate vesicle tethering. Our studies on AP-4 have made use of subcellular proteomics to find AP-4-dependent cargo and machinery, and have revealed a key role in the trafficking of the autophagy protein ATG9 out to the cell periphery. These findings help to explain the AP-4 deficiency phenotype in humans.