Syndapin I is the phosphorylation-regulated dynamin I partner in synaptic vesicle endocytosis.
Syndapin I is the phosphorylation-regulated dynamin I partner in synaptic vesicle endocytosis.
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DOI：
10.1038/nn1695
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发表时间：
2006-06
影响因子：
25
通讯作者：
Robinson, Phillip J
中科院分区：
文献类型：
--
作者：
Anggono, Victor;Smillie, Karen J;Graham, Mark E;Valova, Valentina A;Cousin, Michael A;Robinson, Phillip J
在神经末梢突触囊泡内吞（SVE）过程中，动力蛋白I在Ser-774和Ser-778位点被去磷酸化。磷酸化被认为是调节内吞蛋白复合物与amphiphysin或endophilin的组装。相反，我们发现它为SVE募集突触蛋白I，并且不控制大鼠突触体中两性肽或嗜内啡肽的结合。去极化后，syndapin表现出钙调磷酸酶介导的与动力蛋白的相互作用。一种磷酸化位点模拟肽破坏了动力蛋白-突触蛋白复合物，而不是动力蛋白-亲内肽复合物，在重复刺激后抑制SVE并产生谷氨酸释放疲劳。Ser-774或Ser-778的假磷酸化抑制了syndapin的结合，而不影响两栖蛋白的募集。培养神经元中丙氨酸阻滞SVE的位点突变。这些位点对syndapin I结合和SVE具有加性作用。因此syndapin I是SVE内吞蛋白复合物的核心成分，通过刺激依赖性募集到dynamin I，并在突触传递中起关键作用。
Dynamin I is dephosphorylated at Ser-774 and Ser-778 during synaptic vesicle endocytosis (SVE) in nerve terminals. Phosphorylation was proposed to regulate assembly of an endocytic protein complex with amphiphysin or endophilin. Instead, we found it recruits syndapin I for SVE and does not control amphiphysin or endophilin binding in rat synaptosomes. After depolarisation, syndapin exhibited a calcineurin-mediated interaction with dynamin. A phosphorylation site-mimicking peptide disrupted the dynamin-syndapin complex, not the dynamin-endophilin complex, arrested SVE and produced glutamate release fatigue after repetitive stimulation. Pseudo-phosphorylation of Ser-774 or Ser-778 inhibited syndapin binding without affecting amphiphysin recruitment. Site mutagenesis to alanine arrested SVE in cultured neurons. The effects of the sites were additive for syndapin I binding and SVE. Thus syndapin I is a central component of the endocytic protein complex for SVE via stimulus-dependent recruitment to dynamin I and plays a key role in synaptic transmission.