Cysteine String Protein (CSP) Inhibition of N-type Calcium Channels Is Blocked by Mutant Huntingtin

Show simple item record

dc.contributor.author Miller, Linda C.
dc.contributor.author Swayne, Leigh Anne
dc.contributor.author Chen, Lina
dc.contributor.author Feng, Zhong-Ping
dc.contributor.author Wacker, Jennifer L.
dc.contributor.author Muchowski, Paul J.
dc.contributor.author Zamponi, Gerald W.
dc.contributor.author Braun, Janice E. A.
dc.date.accessioned 2016-04-12T06:26:40Z
dc.date.available 2016-04-12T06:26:40Z
dc.date.copyright 2003 en_US
dc.date.issued 2003
dc.identifier.citation Miller, L.C., Swayne, L.A., Chen, L., Feng, Z-P., Wacker, J.L., Muchowski, P.J., … Braun, E.A. (2003). Cysteine string protein (CSP) inhibition of N-type calcium channels is blocked by mutant huntingtin. The Journal of Biological Chemistry, 278(52), 53072-53081. en_US
dc.identifier.uri http://dx.doi.org/10.1074/jbc.M306230200
dc.identifier.uri http://hdl.handle.net/1828/7102
dc.description.abstract Cysteine string protein (CSP), a 34-kDa molecular chaperone, is expressed on synaptic vesicles in neurons and on secretory vesicles in endocrine, neuroendocrine, and exocrine cells. CSP can be found in a complex with two other chaperones, the heat shock cognate protein Hsc70, and small glutamine-rich tetratricopeptide repeat domain protein (SGT). CSP function is vital in synaptic transmission; however, the precise nature of its role remains controversial. We have previously reported interactions of CSP with both heterotrimeric GTP-binding proteins (G proteins) and N-type calcium channels. These associations give rise to a tonic G protein inhibition of the channels. Here we have examined the effects of huntingtin fragments (exon 1) with (huntingtin exon1/exp) and without (huntingtin exon1/nonexp) expanded polyglutamine (polyQ) tracts on the CSP chaperone system. In vitro huntingtin exon1/exp sequestered CSP and blocked the association of CSP with G proteins. In contrast, huntingtin exon1/nonexp did not interact with CSP and did not alter the CSP/G protein association. Similarly, co-expression of huntingtin exon1/exp with CSP and N-type calcium channels eliminated CSP’s tonic G protein inhibition of the channels, while coexpression of huntingtin exon1/nonexp did not alter the robust inhibition promoted by CSP. These results indicate that CSP’s modulation of G protein inhibition of calcium channel activity is blocked in the presence of a huntingtin fragment with expanded polyglutamine tracts. en_US
dc.description.sponsorship This work was supported by operating grants (to J. E. A. B. and G. W. Z.) from the Canadian Institutes of Health Research (CIHR) and an establishment grant (to J. E. A. B.) from the Alberta Foundation for Medical Research (AHFMR). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Leigh Anne Swayne supported by Natural Science and Engineering Research Council, CIHR, and AHFMR studentships. Zhong-Ping Feng - Recipient of postdoctoral fellowships from CIHR and Heart and Stroke Foundation of Canada. Paul J. Muchowski supported by the Hereditary Disease Foundation under the auspices of the Cure Huntington’s Disease initiative. Gerald W. Zamponi - An AHFMR senior scholar and a CIHR investigator. E.A. Braun - Recipient of a New Investigator award from the CIHR and the Alberta Foundation for Medical Research. To whom correspondence should be addressed: Dept. of Physiology and Biophysics, Cellular and Molecular Neurobiology, University of Calgary, Calgary, Alberta T2N 4N1, Canada. Tel.: 403-220-5463; Fax: 403-283-8731; E-mail: braunj@ucalgary.ca. en_US
dc.language.iso en en_US
dc.publisher The Journal of Biological Chemistry en_US
dc.title Cysteine String Protein (CSP) Inhibition of N-type Calcium Channels Is Blocked by Mutant Huntingtin en_US
dc.type Article en_US
dc.description.scholarlevel Faculty en_US
dc.description.reviewstatus Reviewed en_US

Files in this item

This item appears in the following Collection(s)

Show simple item record

Search UVicSpace


My Account