SYNAPTOTAGMIN-IV IS AN IMMEDIATE-EARLY GENE INDUCED BY DEPOLARIZATIONIN PC12 CELLS AND IN BRAIN

Subtractive library construction and differential screening were used to identify a cDNA for a cell type-specific immediate early gene induc ed in rat PC12 pheochromocytoma cells. Sequencing identified the prote in product of this gene as rat synaptotagmin IV (SytIV). Synaptotagmin s are synaptic vesicle proteins thought to play a role in depolarizati on-induced, calcium-mediated exocytosis and neurotransmitter release. SytIV mRNA accumulation is transiently induced in PC12 cells by potass ium depolarization, calcium ionophore, ATP, and forskolin. In contrast , growth factors and phorbol 12-myristate 13-acetate induce little or no SytIV mRNA accumulation. Kainic acid-induced seizures in rats are f ollowed by accumulation of SytIV message in the hippocampus and pirifo rm cortex. The SytIV gene may provide a direct link between depolariza tion-induced neuronal gene expression and subsequent modulation of syn aptic structure and function.