PIP kinase Iγ is the major PI(4,5)P₂ synthesizing enzyme at the synapse

Disruption of the presynaptically enriched polyphosphoinositide phosphatase synaptojanin 1 leads to an increase of clathrin-coated intermediates and of polymerized actin at endocytic zones of nerve terminals. These changes correlate with elevated levels of PI(4,5)P₂ in neurons. We report that phosphatidylinositol phosphate kinase type Iγ (PIPKIγ), a major brain PI(4)P 5-kinase, is concentrated at synapses. Synaptojanin 1 and PIPKIγ antagonize each other in the recruitment of clathrin coats to lipid membranes. Like synaptojanin 1 and other proteins involved in endocytosis, PIPKIγ undergoes stimulation-dependent dephosphorylation. These results implicate PIPKIγ in the synthesis of a PI(4,5)P₂ pool that acts as a positive regulator of clathrin coat recruitment and actin function at the synapse.