CALCINEURIN INHIBITION OF DYNAMIN-I GTPASE ACTIVITY COUPLED TO NERVE-TERMINAL DEPOLARIZATION
CALCINEURIN INHIBITION OF DYNAMIN-I GTPASE ACTIVITY COUPLED TO NERVE-TERMINAL DEPOLARIZATION
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DOI：
10.1126/science.8052858
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发表时间：
1994-08-12
期刊：
影响因子：
56.9
通讯作者：
ROBINSON, PJ
中科院分区：
文献类型：
--
作者：
LIU, JP;SIM, ATR;ROBINSON, PJ
动力蛋白I是一种神经末梢磷酸蛋白，具有内吞作用所需的内源性鸟苷三磷酸酶(GTPase)活性。在去极化和突触小泡循环的过程中，Dynamin I经历了快速的去磷酸化。在体外，动力蛋白I被发现是钙调神经磷酸酶的高亲和力底物。在低浓度下，钙调神经磷酸酶可使已被蛋白激酶C磷酸化的Dynamin I去磷酸化，这种去磷酸化作用可在体外和神经末梢去极化后抑制Dynamin I GTP酶的活性。在神经末梢，这种作用可被钙调神经磷酸酶抑制剂环孢素A所阻止。这表明，在神经末梢，钙调神经磷酸酶作为钙敏感的开关，使去极化引起的突触小泡循环。
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 Ca2+-sensitive switch for depolarization-evoked synaptic vesicle recycling.