Calcineurin inhibition of dynamin I GTPase activity coupled to nerve terminal depolarization.
Dynamin I is a nerve terminal phosphoprotein with intrinsic guanosine triphosphatase (GTPase) activity that is required for endocytosis. Upon depolarization and synaptic vesicle recycling, dynamin I undergoes a rapid dephosphorylation. Dynamin I was found to be a specific high-affinity substrate for calcineurin in vitro. At low concentrations, calcineurin dephosphorylated dynamin I that had been phosphorylated by protein kinase C. The dephosphorylation inhibited dynamin I GTPase activity in vitro and after depolarization of nerve terminals. The effect in nerve terminals was prevented by the calcineurin inhibitor cyclosporin A. This suggests that in nerve terminals, calcineurin serves as a Ca(2+)-sensitive switch for depolarization-evoked synaptic vesicle recycling.
Liu
J P
JP
Endocrine Unit, John Hunter Hospital, NSW, Australia.
Sim
A T
AT
Robinson
P J
PJ
D000818:Animals; D019703:Calcineurin; D002118:Calcium / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000378:metabolism / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology; D034284:Dynamin I; D034281:Dynamins; D004705:Endocytosis; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009411:Nerve Endings / Q000201:enzymology / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D013572:Synaptic Vesicles / Q000378:metabolism*; D013574:Synaptosomes / Q000201:enzymology / Q000378:metabolism*
D002148:Calmodulin-Binding Proteins; D016572:Cyclosporine; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D034284:Dynamin I; D020558:GTP Phosphohydrolases; D034281:Dynamins; D002118:Calcium