The cell fate determinant numb interacts with EHD/Rme-1 family proteins and has a role in endocytic recycling.
The cell fate determinant numb interacts with EHD/Rme-1 family proteins and has a role in endocytic recycling.
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DOI：
10.1091/mbc.e04-01-0026
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发表时间：
2004-08
影响因子：
3.3
通讯作者：
Christian A. Smith;S. Dho;J. Donaldson;U. Tepass;C. McGlade
中科院分区：
文献类型：
--
作者：
Christian A. Smith;S. Dho;J. Donaldson;U. Tepass;C. McGlade
适配器蛋白麻木对于果蝇神经系统中祖细胞的细胞命运规范是必需的。 Numb在进化上是保守的，以前的研究为哺乳动物发育期间具有相似功能作用提供了证据。麻木蛋白具有多种蛋白质 - 蛋白质相互作用区域，包括磷酸酪氨酸结合（PTB）结构域和一个羧基末端结构域，其中包含保守的相互作用基序，包括EH（EPS15同源性）结构域结合基序和α-Adaptin-Adaptin结合位点。在这项研究中，我们将内吞蛋白质的EHD/RME-1/Pincher家族作为哺乳动物和果蝇中的麻木相互作用伴侣。 EHD/RME-1蛋白在通过网格蛋白介导的内吞作用和通过ADP核糖基化因子6（ARF6）调节的网状介导的内吞作用和非网状蛋白独立途径内化的质膜受体的回收中的作用。在这里，我们报告了与内源性EHD4/Pincher和ARF6的麻木，并且ARF6突变体改变了麻木的亚细胞定位。此外，我们提供了证据表明，麻木在受体的内体回收和细胞内运输中具有新的功能。
The adaptor protein Numb is necessary for the cell fate specification of progenitor cells in the Drosophila nervous system. Numb is evolutionarily conserved and previous studies have provided evidence for a similar functional role during mammalian development. The Numb protein has multiple protein-protein interaction regions including a phosphotyrosine binding (PTB) domain and a carboxy-terminal domain that contains conserved interaction motifs including an EH (Eps15 Homology) domain binding motif and alpha-adaptin binding site. In this study we identify the EHD/Rme-1/Pincher family of endocytic proteins as Numb interacting partners in mammals and Drosophila. The EHD/Rme-1 proteins function in recycling of plasma membrane receptors internalized by both clathrin-mediated endocytosis and a clathrin-independent pathway regulated by ADP ribosylation factor 6 (Arf6). Here we report that Numb colocalizes with endogenous EHD4/Pincher and Arf6 and that Arf6 mutants alter Numb subcellular localization. In addition, we present evidence that Numb has a novel function in endosomal recycling and intracellular trafficking of receptors.