The cysteine string protein multimeric complex.
Cysteine string protein (CSPalpha) is a member of the cellular folding machinery that is located on regulated secretory vesicles. We have previously shown that CSPalpha in association with Hsc70 (70kDa heat shock cognate protein) and SGT (small glutamine-rich tetratricopeptide repeat domain protein) is a guanine nucleotide exchange factor (GEF) for G(alphas). Association of this CSPalpha complex with N-type calcium channels, a channel key in coupling calcium influx with synaptic vesicle exocytosis, triggers tonic G protein inhibition of the channels. Syntaxin 1A, a plasma membrane SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) critical for neurotransmission, coimmunoprecipitates with the CSPalpha/G protein/N-type calcium channel complex, however the significance of syntaxin 1A as a component of this complex remains unknown. In this report, we establish that syntaxin 1A interacts with CSPalpha, Hsc70 as well as the synaptic protein interaction (synprint) region of N-type channels. We demonstrate that huntingtin(exon1), a putative biologically active fragment of huntingtin, displaces both syntaxin 1A and CSPalpha from N-type channels. Identification of the protein components of the CSPalpha/GEF system is essential in establishing its precise role in synaptic transmission.
Swayne
Leigh Anne
LA
Department of Physiology and Biophysics, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
Beck
Katy E
KE
Braun
Janice E A
JE
D000818:Animals; D001665:Binding Sites; D005091:Exons; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050883:HSC70 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D050600:SNARE Proteins / Q000378:metabolism; D009435:Synaptic Transmission; D050827:Syntaxin 1 / Q000737:chemistry* / Q000378:metabolism
D020662:Guanine Nucleotide Exchange Factors; D050883:HSC70 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D050600:SNARE Proteins; D050827:Syntaxin 1; C088460:cysteine string protein