Dr. Jihong Bai
Division of Basic Sciences
Fred Hutchinson Cancer Research Center
Seattle, WA

Friday, October 24, 2014
3:30 pm (CT)
2269 Beckman Institute

Abstract

Synaptic vesicle (SV) endocytosis occurs through rapid and coordinated action of endocytic proteins. A classical example is the functional pair of synaptojanin and endophilin. Synaptojanin is a neuronal phosphoinositide phosphatase that is transiently recruited to endocytic intermediates to facilitate SV recycling. Current models suggest synaptojanin activity is tightly interwoven with endophilin through high affinity binding between the synaptojanin proline-rich domain (PRD) and the endophilin SH3 domain. Biochemical studies suggest that the SH3-PRD interactions are the molecular basis allowing endophilin to bring synaptojanin to endocytic intermediates. In contrast to this view, we find that truncated synaptojanin mutants lacking the PRD domain fully reconstitute synaptic transmission, indicating that synaptojanin’s core function in vivo resides in the remaining two domains: an N-terminal Sac1 phosphatase domain and a central 5-phosphatase domain. Here, I would like to discuss an unexpected role of the Sac1 domain in vivo in supporting coincident action between synaptojanin and endophilin at synapses. Membranes are highly dynamic in all living cells. Numerous proteins act in concert to sculpt membrane organelles into characteristic morphology. Steady-state analyses suggest that these proteins may act as curvature sensors, membrane benders, or scaffolding molecules. Here, we provide a dynamic view on how endophilin, a founding member of the Bin– Amphiphysin–Rvs (BAR) proteins, shapes membranes. I would like to present a time-resolved model describing how endophilin integrates its ability in sensing, bending, and scaffolding to sculpt membranes.