Coated vesicle adaptors (360G-Wellcome-214272_Z_18_Z)

Coated vesicles transport molecules from one membrane compartment of the cell (a donor compartment) to another (acceptor) compartment. Adaptors are the components of the coat that select the vesicle cargo. The adaptor protein complexes AP-1 and AP-2 are associated with clathrin-coated vesicles (CCVs), while APs 3, 4, and 5 appear to be clathrin-independent. I have been working on adaptors for over 35 years, but there are still many unanswered questions. We plan to focus on the following areas: 1. The AP-1 pathway. How are the AP-1 donor organelles related to each other, and how are the vesicles recognised so they fuse with the right acceptor compartment? 2. AP-4, AP-5, and hereditary spastic paraplegia. How do AP-4 and AP-5 select cargo and make vesicles, and why do mutations in either of them cause hereditary spastic paraplegia?