PIP kinase Igamma is the major PI(4,5)P(2) 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)P(2) in neurons. We report that phosphatidylinositol phosphate kinase type Igamma (PIPKIgamma), a major brain PI(4)P 5-kinase, is concentrated at synapses. Synaptojanin 1 and PIPKIgamma antagonize each other in the recruitment of clathrin coats to lipid membranes. Like synaptojanin 1 and other proteins involved in endocytosis, PIPKIgamma undergoes stimulation-dependent dephosphorylation. These results implicate PIPKIgamma in the synthesis of a PI(4,5)P(2) pool that acts as a positive regulator of clathrin coat recruitment and actin function at the synapse.
Wenk
M R
MR
Howard Hughes Medical Institute and Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06511, USA.
Pellegrini
L
L
Klenchin
V A
VA
Di Paolo
G
G
Chang
S
S
Daniell
L
L
Arioka
M
M
Martin
T F
TF
De Camilli
P
P
D000199:Actins / Q000378:metabolism; D000818:Animals; D000906:Antibodies; D001921:Brain / Q000201:enzymology; D002966:Clathrin / Q000378:metabolism; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000096:biosynthesis*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D013570:Synaptic Membranes / Q000201:enzymology / Q000648:ultrastructure; D013572:Synaptic Vesicles / Q000201:enzymology* / Q000648:ultrastructure
D000199:Actins; D000906:Antibodies; D002966:Clathrin; D009419:Nerve Tissue Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase; C097702:synaptojanin; D010744:Phosphoric Monoester Hydrolases