Vesicle uncoating regulated by SH3-SH3 domain-mediated complex formation between endophilin and intersectin at synapses.
Vesicle uncoating regulated by SH3-SH3 domain-mediated complex formation between endophilin and intersectin at synapses.
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DOI：
10.15252/embr.201439260
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发表时间：
2015-02
期刊：
影响因子：
7.7
通讯作者：
Haucke V
中科院分区：
文献类型：
--
作者：
Pechstein A;Gerth F;Milosevic I;Jäpel M;Eichhorn-Grünig M;Vorontsova O;Bacetic J;Maritzen T;Shupliakov O;Freund C;Haucke V
神经传递涉及突触囊泡（SV）膜的外吞-内吞循环。内吞膜修复和网格蛋白介导的SV重组需要曲率敏感和膜弯曲的BAR结构域蛋白，如内啡肽A。虽然它们感知和稳定弯曲膜的能力促进BAR结构域蛋白的膜募集，但它们靶向SV再循环的特定位点的精确机制仍不清楚。在这里，我们证明了多域支架intersectin 1直接与内啡肽A，以促进囊泡在突触的脱壳。intersectin 1缺陷的敲除小鼠在突触处积累网格蛋白包被的囊泡，这是一种类似于内啡肽功能丧失的表型。Intersectin 1/endophilin A1复合物的形成是通过intersectin的SH 3B结构域与endophilin A1的SH 3结构域上的非典型位点的直接结合介导的。与此相一致，interstin结合缺陷突变体内嗜蛋白A1不能拯救来自内嗜蛋白A1-3三重敲除（TKO）小鼠的神经元突触处的网格蛋白积累。我们的数据支持一个模型，其中intersectin艾滋病endophilin A招聘网站网格蛋白介导的SV回收，从而促进囊泡脱壳。
Neurotransmission involves the exo-endocytic cycling of synaptic vesicle (SV) membranes. Endocytic membrane retrieval and clathrin-mediated SV reformation require curvature-sensing and membrane-bending BAR domain proteins such as endophilin A. While their ability to sense and stabilize curved membranes facilitates membrane recruitment of BAR domain proteins, the precise mechanisms by which they are targeted to specific sites of SV recycling has remained unclear. Here, we demonstrate that the multi-domain scaffold intersectin 1 directly associates with endophilin A to facilitate vesicle uncoating at synapses. Knockout mice deficient in intersectin 1 accumulate clathrin-coated vesicles at synapses, a phenotype akin to loss of endophilin function. Intersectin 1/endophilin A1 complex formation is mediated by direct binding of the SH3B domain of intersectin to a non-canonical site on the SH3 domain of endophilin A1. Consistent with this, intersectin-binding defective mutant endophilin A1 fails to rescue clathrin accumulation at neuronal synapses derived from endophilin A1-3 triple knockout (TKO) mice. Our data support a model in which intersectin aids endophilin A recruitment to sites of clathrin-mediated SV recycling, thereby facilitating vesicle uncoating.
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影响因子：
16.2
作者：
Milosevic I;Giovedi S;Lou X;Raimondi A;Collesi C;Shen H;Paradise S;O'Toole E;Ferguson S;Cremona O;De Camilli P
通讯作者：
De Camilli P
影响因子：
11.8
作者：
Chang-Ileto, Belle;Frere, Samuel G.;Chan, Robin B.;Voronov, Sergey V.;Roux, Aurelian;Di Paolo, Gilbert
通讯作者：
Di Paolo, Gilbert
影响因子：
64.5
作者：
Mim C;Cui H;Gawronski-Salerno JA;Frost A;Lyman E;Voth GA;Unger VM
通讯作者：
Unger VM
影响因子：
7.2
作者：
Saheki, Yasunori;De Camilli, Pietro
通讯作者：
De Camilli, Pietro
影响因子：
4
作者：
Sundborger, Anna;Soderblom, Cynthia;Shupliakov, Oleg
通讯作者：
Shupliakov, Oleg