A trimeric protein complex functions as a synaptic chaperone machine

We identify a chaperone complex composed of (1) the synaptic vesicle cystei ne string protein (CSP), thought to function in neurotransmitter release, ( 2) the ubiquitous heat-shock protein cognate Hsc70, and (3) the SGT protein containing three tandem tetratricopeptide repeats. These three proteins in teract with each other to form a stable trimeric complex that is located on the synaptic vesicle surface, and is disrupted in CSP knockout mice. The C SP/SGT/Hsc70 complex functions as an ATP-dependent chaperone that reactivat es a denatured substrate. SGT overexpression in cultured neurons inhibits n eurotransmitter release, suggesting that the CSP/SGT/Hsc70 complex is impor tant for maintenance of a normal synapse. Taken together, our results ident ify a novel trimeric complex that functions as a synapse-specific chaperone machine.