Molecular determinants of cysteine string protein modulation of N-type calcium channels

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dc.contributor.authorMiller, Linda C.
dc.contributor.authorSwayne, Leigh Anne
dc.contributor.authorKay, Jason G.
dc.contributor.authorFeng, Zhong-Ping
dc.contributor.authorJarvis, Scott E.
dc.contributor.authorZamponi, Gerald W.
dc.contributor.authorBraun, Janice E. A.
dc.date.accessioned2016-03-11T13:13:48Z
dc.date.available2016-03-11T13:13:48Z
dc.date.copyright2003en_US
dc.date.issued2003
dc.description.abstractCysteine string proteins (CSPs) are secretory vesicle chaperones that are important for neurotransmitter release. We have previously reported an interaction of CSP with both heterotrimeric GTP-binding proteins (G proteins) and N-type calcium channels that results in a tonic G protein inhibition of the channels. In this report we directly demonstrate that two separate regions of CSP associate with G proteins. The N-terminal binding site of CSP, which includes the J domain, binds Ga subunits but not Gbg subunits whereas the C terminal binding site of CSP associates with either free Gbg subunits or Gbg in complex with Ga. The interaction of either binding site of CSP (CSP1-82 or CSP83-198) with G proteins elicits robust tonic inhibition of N-type calcium channel activity. However, CSP1-82 inhibition and CSP83-198 inhibition of calcium channels occur through distinct mechanisms. Calcium channel inhibition by CSP83-198 (but not CSP1-82) is completely blocked by co-expression of the synaptic protein interaction site (synprint) of the N-type channel, indicating that CSP83-198 inhibition is dependent on a physical interaction with the calcium channel. These results suggest that distinct binding sites of CSP can play a role in modulating G protein function and G protein inhibition of calcium channels.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipThis work was supported by operating grants to J.B. and G.W.Z. from the Canadian Institute of Health research (CIHR) and an establishment grant to J.B. from the Alberta Foundation for Medical Research. J.B. holds faculty Scholarships from the CIHR and the Alberta Heritage Foundation for Medical Research (AHFMR). G.W.Z. is an AHFMR senior scholar and a CIHR investigator. L.A.S. is supported by an NSERC studentship. S.E.J. is supported by an AHFMR studentship. Z.P.F. holds postdoctoral fellowships from CIHR and Heart and Stroke Foundation of Canada.en_US
dc.identifier.citationMiller, L.C., Swayne, L.A., Kay, J.G., Feng, Z-P., Jarvis, S.E., Zamponi, G.W. & Braun, J.E.A. (2003). Molecular determinants of cysteine string protein modulation of N-type calcium channels. Journal of Cell Science, 116(14), 2967-2974.en_US
dc.identifier.urihttp://dx.doi.org/10.1242/jcs.00595
dc.identifier.urihttp://hdl.handle.net/1828/7072
dc.language.isoenen_US
dc.publisherJournal of Cell Scienceen_US
dc.subjectCysteine string protein
dc.subjectChaperones
dc.subjectG proteins
dc.subjectN-type calcium channels
dc.subjectSynaptic transmission
dc.subjectJ domain
dc.subject.departmentDivision of Medical Sciences
dc.subject.departmentSchool of Medical Sciences
dc.titleMolecular determinants of cysteine string protein modulation of N-type calcium channelsen_US
dc.typeArticleen_US

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