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 f unction is formed. We report here that the formation of this complex is med iated 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-term inal 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.