Syndapin I is the phosphorylation-regulated dynamin I partner in synaptic vesicle endocytosis

被引：172
作者：
Anggono, Victor
Smillie, Karen J.
Graham, Mark E.
Valova, Valentina A.
Cousin, Michael A.
Robinson, Phillip J.
机构：
[1] Childrens Med Res Inst, Cell Signalling Unit, Wentworthville, NSW 2145, Australia
[2] Univ Edinburgh, Membrane Biol Grp, Ctr Integrat Physiol, Edinburgh EH8 9XD, Midlothian, Scotland
来源：
NATURE NEUROSCIENCE | 2006年 / 9卷 / 06期
基金：
英国惠康基金;
关键词：
D O I：
10.1038/nn1695
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Dynamin I is dephosphorylated at Ser-774 and Ser-778 during synaptic vesicle endocytosis (SVE) in nerve terminals. Phosphorylation was proposed to regulate the 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 depolarization, syndapin showed a calcineurin-mediated interaction with dynamin. A peptide mimicking the phosphorylation sites disrupted the dynamin-syndapin complex, not the dynamin-endophilin complex, arrested SVE and produced glutamate release fatigue after repetitive stimulation. Pseudophosphorylation 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 has a key role in synaptic transmission.
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收藏
页码：752 / 760
页数：9
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