Developmental regulation and specific brain distribution of phosphorabphilin

Protein kinases and phosphatases play an important role in modulating synap tic transmission. The synaptic protein rabphilin associates with synaptic v esicles through the small GTPase Rab3A, binds Ca2+ and phospholipids, and i nteracts with cytoskeletal elements, yet its function remains controversial . In this study, we have generated phosphospecific antibodies and studied t he developmental, subcellular, and brain distribution of rabphilin phosphor ylated at serine-234 and serine-274. Our results show that phosphorabphilin is present in vivo under basal conditions in a specific subset of synapses . The phosphorylated rabphilin is abundant in the cerebellum, midbrain, and medulla; phosphorabphilin is specifically enriched in the climbing fiber s ynapses of the cerebellar cortex. Its developmental profile reveals a sharp and transient increase at approximately postnatal day 16, a period critica l for the activity-dependent pruning of supernumerary climbing fibers in th e cerebellum. We propose that the phosphorylation of rabphilin regulates ne uronal activity through development and in a synapse-specific manner.