Two distinct domains in hsc70 are essential for the interaction with the synaptic vesicle cysteine string protein

The cysteine string protein (csp) is a synaptic vesicle protein found to be essential for normal neurotransmitter release. The precise function of csp in the synaptic vesicle cycle is still enigmatic. By interacting with the heat-shock cognate hsc70, a cochaperone-chaperone complex with an unknown function is formed. We report here that the formation of this complex is mediated by two distinct domains in hsc70. The ATPase domain and the substrate-binding domain must cooperate to create a binding site for csp. The C-terminal domain of hsc70 seems to function as a regulator for the formation of the cochaperone-chaperone complex. We also show that the interaction of csp with heat-shock proteins is confined to hsc70 and hsp70. Other heat-shock proteins, like hsp60 and hsp90, do not interact with csp.