Phosphoinositides in membrane traffic at the synapse

Inositol phospholipids represent a minor fraction of membrane phospholipids; yet they play important regulatory functions in signaling pathways and membrane traffic. The phosphorylated inositol ring can act either as a precursor for soluble intracellular messengers or as a binding site for cytosolic or membrane proteins. Hence, phosphorylation-dephosphorylation of phosphoinositides represents a mechanism for regulation of recruitment to the membrane of coat proteins, cytoskeletal scaffolds or signaling complexes and for the regulation of membrane proteins. Recent work suggests that phosphoinositide metabolism has an important role in membrane traffic at the synapse. PtdIns(4,5)P2 generation is implicated in the secretion of at least a subset of neurotransmitters. Furthermore, PtdIns(4,5)P2 plays a role in the nucleation of clathrin coats and of an actin-based cytoskeletal scaffold at endocytic zones of synapses, and PtdIns(4,5)P2 dephosphorylation accompanies the release of newly formed vesicles from these interactions. Thus, the reversible phosphorylation of inositol phospholipids may be one of the mechanisms governing the timing and vectorial progression of synaptic vesicle membranes during their exocytic-endocytic cycle.