Cysteine string protein regulates G protein modulation of N-type calcium channels

Cysteine string proteins (CSPs) are secretory vesicle proteins bearing a "J domain" and a palmitoylated cysteine-rich "string" region that are critica l for neurotransmitter release. The precise role of CSP in neurotransmissio n is controversial. Here, we demonstrate a novel interaction between CSP, r eceptor-coupled trimeric GTP binding proteins (G proteins), and N-type Ca2 channels. G(alpha) subunits interact with the J domain of CSP in an ATP-de pendent manner; in contrast, G(beta gamma) subunits interact with the C ter minus of CSP in both the presence and absence of ATP. The interaction of CS P with both G proteins and N-type Ca2+ channels results in a tonic G protei n inhibition of the channels. In view of the crucial importance of N-type C a2+ channels in presynaptic Vesicle release, our data attribute a key role to CSP in the fine tuning of neurotransmission.