The CSPα/G protein complex in PC12 cells

Cysteine string proteinα (CSPα) 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 CSPα and heterotrimeric GTP binding protein (G protein) signal transduction pathways. We have shown that CSPα is a guanine nucleotide exchange factor (GEF) for G αs. In vitro Hsc70 (70 kDa heat shock cognate protein) and SGT (small glutamine-rich tetratricopeptide repeat domain protein) switch CSPα from an inactive GEF to an active GEF. Here we have examined the cellular distribution of the CSPα system in the PC12 neuroendocrine cell line. CSPα, an established secretory vesicle protein, was found to concentrate in the processes of NGF-differentiated PC12 cells as expected. G β subunits co-localized and G αs subunits partially co-localized with CSPα. However, under the conditions examined, the GEF activity of CSPα is expected to be inactive, in that Hsc70 was not found in PC12 processes. These results indicate that CSPα activity is subject to regulation by factors that alter Hsc70 distribution and translocation within the cell.