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

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.