PAT1, a microtubule-interacting protein, recognizes the basolateral sorting signal of amyloid precursor protein
PAT1, a microtubule-interacting protein, recognizes the basolateral sorting signal of amyloid precursor protein
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DOI：
10.1073/pnas.95.25.14745
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发表时间：
1998-12-08
影响因子：
11.1
通讯作者：
Pimplikar, SW
中科院分区：
文献类型：
--
作者：
Zheng, PZ;Eastman, J;Pimplikar, SW
在上皮细胞中，膜蛋白在基底外侧表面的分选取决于其细胞质域中基底外侧分选信号（BaSS）的存在。淀粉样前体蛋白（APP）是一种与阿尔茨海默病发病机制有关的基底外侧蛋白，含有基于酪氨酸的BaSS，酪氨酸残基的突变导致APP的非极化运输。在这里，我们报告了一种名为 PAT1（与 APP 尾部 1 相互作用的蛋白质）的蛋白质的鉴定，该蛋白质与 APP-BaSS 相互作用，但当关键酪氨酸发生突变时，结合效果很差，并且不结合 APP 基于酪氨酸的内吞信号。 PAT1 与驱动蛋白轻链具有同源性，驱动蛋白轻链是参与将膜蛋白转运至基底外侧表面的正端定向微管马达的组成部分。 PAT1 是一种细胞质蛋白，与膜结合，与含有 APP 的囊泡共分级，并以核苷酸敏感的方式结合微管。 PAT1与报告蛋白的共转染表明PAT1与APP的细胞内转运在功能上相关，我们推测PAT1参与APP沿着微管向细胞表面的易位。
In epithelial cells, sorting of membrane proteins to the basolateral surface depends on the presence of a basolateral sorting signal (BaSS) in their cytoplasmic domain. Amyloid precursor protein (APP), a basolateral protein implicated in the pathogenesis of Alzheimer's disease, contains a tyrosine-based BaSS, and mutation of the tyrosine residue results in nonpolarized transport of APP. Here we report identification of a protein, termed PAT1 (protein interacting with APP tail 1), that interacts with the APP-BaSS but binds poorly when the critical tyrosine is mutated and does not bind the tyrosine-based endocytic signal of APP. PAT1 shows homology to kinesin light chain, which is a component of the plus-end directed microtubule-based motor involved in transporting membrane proteins to the basolateral surface. PAT1, a cytoplasmic protein, associates with membranes, cofractionates with APP-containing vesicles, and binds microtubules in a nucleotide-sensitive manner. Cotransfection of PAT1 with a reporter protein shows that PAT1 is functionally linked with intracellular transport of APP, We propose that PAT1 is involved in the translocation of APP along microtubules toward the cell surface.