Cysteine String Protein Regulates G Protein Modulation of N-Type Calcium Channels

• Published in: Neuron (Cambridge, Mass.) Vol. 28; no. 1; pp. 195 - 204
• Main Authors: Magga, Johanna M., Jarvis, Scott E., Arnot, Michelle I., Zamponi, Gerald W., Braun, Janice E.A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2000
• Subjects: Adenosine Triphosphate - metabolism; Animals; Calcium Channel Blockers - pharmacology; Calcium Channels, N-Type - drug effects; Calcium Channels, N-Type - metabolism; Cell Line; Cross-Linking Reagents - pharmacology; cysteine string proteins; GTP-Binding Proteins - genetics; GTP-Binding Proteins - metabolism; GTP-Binding Proteins - pharmacology; Hippocampus - chemistry; Hippocampus - metabolism; HSP40 Heat-Shock Proteins; Humans; Immunoblotting; In Vitro Techniques; Ion Transport - drug effects; Membrane Proteins - drug effects; Membrane Proteins - metabolism; Models, Molecular; Patch-Clamp Techniques; Potassium Chloride - pharmacology; Protein Binding - drug effects; Protein Subunits; Rats
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(00)00096-9

Cysteine string proteins (CSPs) are secretory vesicle proteins bearing a “J domain” and a palmitoylated cysteine-rich “string” region that are critical for neurotransmitter release. The precise role of CSP in neurotransmission is controversial. Here, we demonstrate a novel interaction between CSP, receptor-coupled trimeric GTP binding proteins (G proteins), and N-type Ca 2+ channels. G α subunits interact with the J domain of CSP in an ATP-dependent manner; in contrast, G βγ subunits interact with the C terminus of CSP in both the presence and absence of ATP. The interaction of CSP with both G proteins and N-type Ca 2+ channels results in a tonic G protein inhibition of the channels. In view of the crucial importance of N-type Ca 2+ channels in presynaptic vesicle release, our data attribute a key role to CSP in the fine tuning of neurotransmission.