Phosphorylation of a Synaptic Vesicle-associated Protein by an Inositol Hexakisphosphate-regulated Protein Kinase

Abstract

Despite the fact that inositol hexakisphosphate (InsP6) is the most abundant inositol metabolite in cells, its cellular function has remained an enigma. In the present study, we present the first evidence of a protein kinase identified in rat cerebral cortex/hippocampus that is activated by InsP6. The substrate for the InsP6-regulated protein kinase was found to be the synaptic vesicle-associated protein, pacsin/syndapin I. This brain-specific protein, which is highly enriched at nerve terminals, is proposed to act as a molecular link coupling components of the synaptic vesicle endocytic machinery to the cytoskeleton. We show here that the association between pacsin/syndapin I and dynamin I can be increased by InsP 6-dependent phosphorylation of pacsin/syndap in I. These data provide a model by which InsP6-dependent phosphorylation regulates synaptic vesicle recycling by increasing the interaction between endocytic proteins at the synapse.