Syndapin I, a synaptic dynamin binding protein that associates with the neural Wiskott-Aldrich syndrome protein
Syndapin I, a synaptic dynamin binding protein that associates with the neural Wiskott-Aldrich syndrome protein
复制标题
DOI：
10.1091/mbc.10.2.501
复制
发表时间：
1999-02-01
影响因子：
3.3
通讯作者：
Kelly, RB
中科院分区：
文献类型：
--
作者：
Qualmann, B;Roos, J;Kelly, RB
GTPase动力蛋白已被明确地与网格蛋白介导的突触囊泡膜在突触前神经末梢的内吞作用有关。在这里，我们描述了一个新的52-kDa蛋白在大鼠脑结合脯氨酸丰富的动力蛋白C端。Syndapin I（突触，动力蛋白相关蛋白I）在大脑中高度富集，以高分子量复合物的形式存在。Syndapin I可以通过C末端的src同源3 （SH3）结构域和两个预测的卷曲线圈拉伸参与多种蛋白质-蛋白质相互作用。共沉淀研究和印迹覆盖分析表明syndapin I通过SH3结构域特异性相互作用结合脑特异性蛋白dynamin I、synaptojanin和synapsin I。动力蛋白I与识别syndapin I的抗体的共免疫沉淀以及syndapin I与动力蛋白I在初级神经元囊泡结构中的共定位表明syndapin I在体内与动力蛋白I结合，可能在突触囊泡内吞作用中发挥作用。此外，syndapin I与神经Wiskott-Aldrich综合征蛋白相关，这是一种调节细胞骨架重排的肌动蛋白解聚蛋白。突触蛋白1的这些特征表明细胞骨架动力学和神经末梢突触囊泡循环之间存在分子联系。
The GTPase dynamin has been clearly implicated in clathrin-mediated endocytosis of synaptic vesicle membranes at the presynaptic nerve terminal. Here we describe a novel 52-kDa protein in rat brain that binds the proline-rich C terminus of dynamin. Syndapin I (synaptic, dynamin-associated protein I) is highly enriched in brain where it exists in a high molecular weight complex. Syndapin I can be involved in multiple protein-protein interactions via a src homology 3 (SH3) domain at the C terminus and two predicted coiled-coil stretches. Coprecipitation studies and blot overlay analyses revealed that syndapin I binds the brain-specific proteins dynamin I, synaptojanin, and synapsin I via an SH3 domain-specific interaction. Coimmunoprecipitation of dynamin I with antibodies recognizing syndapin I and colocalization of syndapin I with dynamin I at vesicular structures in primary neurons indicate that syndapin I associates with dynamin I in vivo and may play a role in synaptic vesicle endocytosis. Furthermore, syndapin I associates with the neural Wiskott-Aldrich syndrome protein, an actin-depolymerizing protein that regulates cytoskeletal rearrangement. These characteristics of syndapin I suggest a molecular link between cytoskeletal dynamics and synaptic vesicle recycling in the nerve terminal.