Phosphorylation of cysteine string protein in the brain: developmental, regional and synaptic specificity.
Protein phosphorylation modulates regulated exocytosis in most cells, including neurons. Cysteine string protein (CSP) has been implicated in this process because its phosphorylation on Ser10 alters its interactions with syntaxin and synaptotagmin, and because the effect of CSP overexpression on exocytosis kinetics in chromaffin cells requires phosphorylatable Ser10. To characterize CSP phosphorylation in the brain, we raised phosphospecific antibodies to Ser10. Western blotting revealed that the proportion of phosphorylated CSP (P-CSP) varies between distinct brain regions and also exhibits developmental regulation, with P-CSP highest early in development. Immunohistochemical analysis of the cerebellar cortex revealed a novel pool of P-CSP that did not colocalize with synaptic vesicle markers during early development. Strikingly, in the adult cerebellar granular layer P-CSP was highly enriched in a subset of glutamatergic synapses but undetectable in neighbouring GABA-ergic synapses. In view of the functional consequences of CSP phosphorylation, such differences could contribute to the synapse-specific regulation of neurotransmitter release.
Evans
Gareth J O
GJ
The Physiological Laboratory, School of Biomedical Sciences, University of Liverpool, Liverpool L69 3BX, UK.
Morgan
Alan
A
D000375:Aging; D000818:Animals; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000502:physiology*; D001933:Brain Stem / Q000254:growth & development / Q000502:physiology; D002531:Cerebellum / Q000502:physiology; D002540:Cerebral Cortex / Q000254:growth & development / Q000502:physiology; D050956:HSP40 Heat-Shock Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009928:Organ Specificity; D010766:Phosphorylation; D051381:Rats; D013569:Synapses / Q000502:physiology*
D050956:HSP40 Heat-Shock Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C088460:cysteine string protein