Coated vesicle adaptors. (360G-Wellcome-086598_Z_08_A)

Adaptors select cargo for inclusion into different types of coated transport vesicles. The best characterised of the adaptors are the AP-1 and AP-2 complexes, which are associated with clathrin-coated vesicles (CCVs) budding from intracellular membranes and from the plasma membrane respectively. We plan to look for new cargo sorting signals using libraries of random cytoplasmic tails, and for new sorting machinery using a combination of CCV proteomics and genome-wide siRNA library screening. In teractions between sorting signals and candidate adaptors will be investigated both structurally (in collaboration with David Owen) and functionally, using a number of novel assays such as CCV profiling and rapid inactivation of CCV machinery by rerouting to mitochondria. Questions we will address include how the GGA pathway interfaces with the AP-1 pathway, how SNAREs are sorted into CCVs, whether GGA-mediated trafficking contributes to the pathology of Alzheimer's disease, and how HIV-1 Nef hi jacks adaptors to down regulate MHC Class I and CD4 from the surface of virally infected cells.