Phyllis I. Hanson
Membrane Trafficking at the Synapse
Stimulated release of neurotransmitter from synaptic vesicles is the fundamental process underlying intercellular communication in the nervous system. Our interests are in building a molecular understanding of membrane trafficking at the synapse. We use biochemical, biophysical and cell biological approaches to study protein-protein and protein-membrane interactions involved in synaptic vesicle docking, fusion and reformation. This work will help advance understanding of synaptic function and its plasticity and will address the more general question of how intracellular membrane fusion reactions are catalyzed.
A number of proteins that participate in exocytosis have been identified, including the synaptic vesicle protein synaptobrevin and the plasma membrane proteins syntaxin and SNAP-25. These three proteins are referred to collectively as SNAREs (soluble NSF-attachment protein receptors), and are representative of families of related proteins that function at different membrane trafficking steps throughout the cell. The three SNAREs bind tightly to each other to form a SNARE complex that interconnects membranes destined to fuse with each other. SNARE complexes are stable unless dissociated by the ATPase NSF (N-ethylmaleimide sensitive fusion protein), and cyclic assembly and disassembly of SNARE complexes is correlated with membrane fusion in vivo. However, it remains unclear exactly how these reactions are linked to membrane fusion. Our efforts are aimed at understanding how these proteins work together and with other factors to bring about such membrane fusion.