title: The CSPalpha/G protein complex in PC12 cells.
abstract: Cysteine string proteinalpha (CSPalpha) is a regulated vesicle protein and molecular chaperone that has been found to be critical for continuous synaptic transmission and is implicated in the defense against neurodegeneration. Previous work has revealed links between CSPalpha and heterotrimeric GTP binding protein (G protein) signal transduction pathways. We have shown that CSPalpha is a guanine nucleotide exchange factor (GEF) for Galphas. In vitro Hsc70 (70 kDa heat shock cognate protein) and SGT (small glutamine-rich tetratricopeptide repeat domain protein) switch CSPalpha from an inactive GEF to an active GEF. Here we have examined the cellular distribution of the CSPalpha system in the PC12 neuroendocrine cell line. CSPalpha, an established secretory vesicle protein, was found to concentrate in the processes of NGF-differentiated PC12 cells as expected. Gbeta subunits co-localized and Galphas subunits partially co-localized with CSPalpha. However, under the conditions examined, the GEF activity of CSPalpha is expected to be inactive, in that Hsc70 was not found in PC12 processes. These results indicate that CSPalpha activity is subject to regulation by factors that alter Hsc70 distribution and translocation within the cell.
authors.affiliation: Hotchkiss Brain Institute, Department of Physiology and Biophysics, University of Calgary, Calgary, Alta., Canada T2N 4N1.
authors.forename: Liping
authors.initials: L
authors.lastname: Bai
authors.forename: Leigh Anne
authors.initials: LA
authors.lastname: Swayne
authors.forename: Janice E A
authors.initials: JE
authors.lastname: Braun
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015870:Gene Expression; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000494:pharmacology; D016716:PC12 Cells; D011485:Protein Binding; D051381:Rats; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D050883:HSC70 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins; D008565:Membrane Proteins; D016708:Synaptophysin; C088460:cysteine string protein; D020932:Nerve Growth Factor; D019204:GTP-Binding Proteins