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 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 Ca2+ channels. G. subunits interact with the J domain of CSP in an ATP-dependent manner; in contrast, Gbetagamma 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 Ca2+ channels results in a tonic G protein inhibition of the channels. In view of the crucial importance of N-type Ca2+ channels in presynaptic vesicle release, our data attribute a key role to CSP in the fine tuning of neurotransmission.
Magga
J M
JM
Department of Physiology and Biophysics, University of Calgary, Alberta, Canada.
Jarvis
S E
SE
Arnot
M I
MI
Zamponi
G W
GW
Braun
J E
JE
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D003432:Cross-Linking Reagents / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D050956:HSP40 Heat-Shock Proteins; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism*; D008958:Models, Molecular; D018408:Patch-Clamp Techniques; D011189:Potassium Chloride / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D021122:Protein Subunits; D051381:Rats
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D003432:Cross-Linking Reagents; D050956:HSP40 Heat-Shock Proteins; D008565:Membrane Proteins; D021122:Protein Subunits; C088460:cysteine string protein; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D019204:GTP-Binding Proteins