Intersectin 1 forms complexes with SGIP1 and Reps1 in clathrin-coated pits
Intersectin 1 forms complexes with SGIP1 and Reps1 in clathrin-coated pits
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DOI：
10.1016/j.bbrc.2010.10.045
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发表时间：
2010-11-12
影响因子：
3.1
通讯作者：
Rynditch, Alla
中科院分区：
文献类型：
--
作者：
Dergai, Oleksandr;Novokhatska, Olga;Rynditch, Alla
Intersectin 1 (ITSN1) 是一种进化上保守的接头蛋白，参与网格蛋白介导的内吞作用、细胞信号传导和细胞骨架重排。 ITSN1基因位于人类21号染色体唐氏综合症关键区域。多项研究证实了 ITSN1 在唐氏综合症表型中的作用。在这里，我们报告了这种内吞适配器相互作用网络中新颖互连的识别。我们发现膜变形蛋白 SGIP1（Src 同源 3 结构域生长因子受体结合 2 样（内亲素）相互作用蛋白 1）和信号转导接头 Reps1（RalBP 相关 Eps1l5 同源结构域蛋白）在体内与 ITSN1 相互作用。这两种相互作用都是由 ITSN1 的 SH3 结构域和蛋白质伴侣富含脯氨酸的基序介导的。此外，还鉴定了包含 SGIP1、Reps1 和 ITSN1 的复合物。我们还发现了 SGIP1 之间的新相互作用。 Reps1 和包含 BAR (Bin/amphiphyn/Rvs) 结构域的蛋白两栖蛋白 1。免疫荧光数据表明，ITSN1 与新鉴定的蛋白质伴侣在网格蛋白包被的凹坑中共定位。这些发现扩展了 ITSN1 作为将内吞复合物成分聚集在一起的支架分子的作用。 (C) 2010 Elsevier Inc. 保留所有权利。
Intersectin 1 (ITSN1) is an evolutionarily conserved adaptor protein involved in clathrin-mediated endocytosis, cellular signaling and cytoskeleton rearrangement. ITSN1 gene is located on human chromosome 21 in Down syndrome critical region. Several studies confirmed role of ITSN1 in Down syndrome phenotype. Here we report the identification of novel interconnections in the interaction network of this endocytic adaptor. We show that the membrane-deforming protein SGIP1 (Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1) and the signaling adaptor Reps1 (RalBP associated Eps1l5-homology domain protein) interact with ITSN1 in vivo. Both interactions are mediated by the SH3 domains of ITSN1 and proline-rich motifs of protein partners. Moreover complexes comprising SGIP1, Reps1 and ITSN1 have been identified. We also identified new interactions between SGIP1. Reps1 and the BAR (Bin/amphiphysin/Rvs) domain-containing protein amphiphysin 1. Immunofluorescent data have demonstrated colocalization of ITSN1 with the newly identified protein partners in clathrin-coated pits. These findings expand the role of ITSN1 as a scaffolding molecule bringing together components of endocytic complexes. (C) 2010 Elsevier Inc. All rights reserved.