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

Journal of Cell Science
Linda C MillerJ E Braun

Abstract

Cysteine 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 Galpha subunits but not Galphabeta subunits whereas the C terminal binding site of CSP associates with either free Galphabeta subunits or Galphabeta in complex with Galpha. 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...Continue Reading

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Citations

Apr 1, 2010·Molecular Neurobiology·Tom Z LuZhong-Ping Feng
Jul 3, 2008·Cell Stress & Chaperones·Alma Rosales-HernandezJanice E A Braun
Aug 15, 2013·Archives of Biochemistry and Biophysics·Hiromi ShimomuraTomoko Nashida
May 11, 2010·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Jadah N JohnsonJanice E A Braun
Oct 7, 2008·Annual Review of Pharmacology and Toxicology·Denis J DupréTerence E Hébert
Mar 14, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Ning WengGuy E Groblewski
Sep 16, 2005·Molecular and Cellular Neurosciences·Leigh Anne SwayneJanice E A Braun
Feb 7, 2012·Progress in Neurobiology·Katherine M BetkeHeidi E Hamm
Aug 1, 2006·Biochemical and Biophysical Research Communications·Leigh Anne SwayneJanice E A Braun
Nov 23, 2006·Biochemical and Biophysical Research Communications·Liping BaiJanice E A Braun
Jan 9, 2007·Biochemical and Biophysical Research Communications·Leigh Anne Swayne, Janice E A Braun
Mar 25, 2015·Seminars in Cell & Developmental Biology·Robert D Burgoyne, Alan Morgan
Dec 15, 2010·Channels·Kevin P M Currie
May 9, 2014·Frontiers in Cellular Neuroscience·Julien Donnelier, Janice E A Braun
Oct 23, 2003·The Journal of Biological Chemistry·Linda C MillerJanice E A Braun
Jun 24, 2005·The Journal of Biological Chemistry·Michael NatochinJanice E A Braun
Nov 30, 2006·Pharmacological Reviews·H William Tedford, Gerald W Zamponi
Mar 17, 2007·The Journal of Biological Chemistry·Denis J DupréTerence E Hébert
Jun 30, 2010·Journal of Neurogenetics·Konrad E Zinsmaier
Jul 2, 2003·Journal of Pharmacological Sciences·Gerald W Zamponi
Feb 12, 2020·Progress in Neurobiology·Cameron B Gundersen

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