Role of dynactin in endocytic traffic: Effects of dynamitin overexpression and colocalization with CLIP-170
Role of dynactin in endocytic traffic: Effects of dynamitin overexpression and colocalization with CLIP-170
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DOI：
10.1091/mbc.10.12.4107
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发表时间：
1999-12-01
影响因子：
3.3
通讯作者：
Schroer, TA
中科院分区：
文献类型：
--
作者：
Valetti, C;Wetzel, DM;Schroer, TA
物质从外周、早期内体到晚期内体的流动需要微管，并且被认为是由负末端定向的运动细胞质动力蛋白及其激活剂动力蛋白促进的。微管结合蛋白CLIP-170也可能通过提供与内体的早期连接而发挥作用。在这里，我们表明，扰动的dynactin功能在体内影响内体动力学和贩运。通常是双向的内体运动被完全抑制。受体介导的摄取和再循环正常发生，但细胞对包膜病毒的感染不太敏感，这些病毒需要：递送到晚期内体，并且它们显示溶酶体靶向探针的积累减少。Dynactin以依赖于CLIP-170的推定的货物结合结构域的方式与CLIP-170共定位在微管正末端。使用p150（Glued），动力肌动蛋白的微管结合亚基，以及CLIP-170的突变体和野生型形式进行的过表达研究表明，CLIP-170将动力肌动蛋白募集到微管末端。这些数据提出了一个新的模型，形成运动复合物的内吞途径的早期内体和微管。
The flow of material from peripheral, early endosomes to-late endosomes requires microtubules and is thought to be facilitated by the minus end-directed motor cytoplasmic dynein and its activator dynactin. The microtubule-binding protein CLIP-170 may also play a role by providing an early link to endosomes. Here, we show that perturbation of dynactin function in vivo affects endosome dynamics and trafficking. Endosome movement, which is normally bidirectional, is completely inhibited. Receptor-mediated uptake and recycling occur normally, but cells are less susceptible to infection by enveloped viruses that require: delivery to late endosomes, and they show reduced accumulation of lysosomally targeted probes. Dynactin colocalizes at microtubule plus ends with CLIP-170 in a way that depends on CLIP-170's putative cargo-binding domain. Overexpression studies using p150(Glued), the microtubule-binding subunit of dynactin, and mutant and wild-type forms of CLIP-170 indicate that CLIP-170 recruits dynactin to microtubule ends. These data suggest a new model for the formation of motile complexes of endosomes and microtubules early in the endocytic pathway.