Department of Biochemistry and Molecular Biology, the Uniformed Services University, Bethesda, MD 20814, USA.
J Cell Biol. 2011 Jun 27;193(7):1245-55. doi: 10.1083/jcb.201011022.
Cytoplasmic dynein transports various cellular cargoes including early endosomes, but how dynein is linked to early endosomes is unclear. We find that the Aspergillus nidulans orthologue of the p25 subunit of dynactin is critical for dynein-mediated early endosome movement but not for dynein-mediated nuclear distribution. In the absence of NUDF/LIS1, p25 deletion abolished the localization of dynein-dynactin to the hyphal tip where early endosomes abnormally accumulate but did not prevent dynein-dynactin localization to microtubule plus ends. Within the dynactin complex, p25 locates at the pointed end of the Arp1 filament with Arp11 and p62, and our data suggest that Arp11 but not p62 is important for p25-dynactin association. Loss of either Arp1 or p25 significantly weakened the physical interaction between dynein and early endosomes, although loss of p25 did not apparently affect the integrity of the Arp1 filament. These results indicate that p25, in conjunction with the rest of the dynactin complex, is important for dynein-early endosome interaction.
细胞质动力蛋白将各种细胞货物包括早期内体运输，但动力蛋白与早期内体如何连接尚不清楚。我们发现，青霉属纽形虫 dynactin 的 p25 亚基的直系同源物对于动力蛋白介导的早期内体运动至关重要，但对于动力蛋白介导的核分布不重要。在没有 NUDF/LIS1 的情况下，p25 缺失消除了动力蛋白 dynactin 到菌丝尖端的定位，在那里早期内体异常积累，但不阻止动力蛋白 dynactin 定位到微管正极。在 dynactin 复合物中，p25 位于 Arp1 丝的尖端，与 Arp11 和 p62 一起，我们的数据表明 Arp11 但不是 p62 对 p25-dynactin 结合很重要。Arp1 或 p25 的缺失都显著削弱了动力蛋白和早期内体之间的物理相互作用，尽管 p25 的缺失并没有明显影响 Arp1 丝的完整性。这些结果表明，p25 与 dynactin 复合物的其余部分一起，对于动力蛋白-早期内体相互作用很重要。
