HookA is a novel dynein-early endosome linker critical for cargo movement in vivo.

HookA is a novel dynein-early endosome linker critical for cargo movement in vivo.
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DOI:
10.1083/jcb.201308009
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发表时间:
2014-03-17
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Xiang X
Xiang X
中科院分区:
其他
文献类型:
--
作者:
Zhang J;Qiu R;Arst HN Jr;Peñalva MA;Xiang X

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HookA是一种新的连接蛋白,它与内体和动力蛋白-动力肌动蛋白结合,并促进曲霉中动力蛋白-早期内体相互作用。胞质动力蛋白可沿沿着微管转运膜质内的货物,但其相互作用的机制尚不清楚。从遗传筛选,我们确定了人类钩蛋白,HookA,作为一个因素所需的动力蛋白介导的早期内体运动的丝状真菌构巢曲霉同源。HookA包含一个假定的N-末端微管结合域,随后是卷曲螺旋域和C-末端货物结合域,这是一种让人联想到细胞质接头蛋白的组织。HookA-早期内体相互作用独立于动力蛋白-早期内体相互作用发生,并且需要C-末端结构域。重要的是,HookA与动力蛋白和动力蛋白相互作用独立于HookA-早期内体相互作用,但依赖于HookA的N-末端部分。HookA和动力蛋白-动力蛋白之间的相互作用需要动力蛋白和动力蛋白的p25亚基,HookA的缺失显著减弱了动力蛋白-早期内体的相互作用,导致早期内体运动几乎完全缺失。因此,HookA是体内动力蛋白-早期内体相互作用的重要的新型接头。
HookA is a novel linker protein that binds to endosomes and to dynein–dynactin and promotes dynein–early endosome interaction in Aspergillus. Cytoplasmic dynein transports membranous cargoes along microtubules, but the mechanism of dynein–cargo interaction is unclear. From a genetic screen, we identified a homologue of human Hook proteins, HookA, as a factor required for dynein-mediated early endosome movement in the filamentous fungus Aspergillus nidulans. HookA contains a putative N-terminal microtubule-binding domain followed by coiled-coil domains and a C-terminal cargo-binding domain, an organization reminiscent of cytoplasmic linker proteins. HookA–early endosome interaction occurs independently of dynein–early endosome interaction and requires the C-terminal domain. Importantly, HookA interacts with dynein and dynactin independently of HookA–early endosome interaction but dependent on the N-terminal part of HookA. Both dynein and the p25 subunit of dynactin are required for the interaction between HookA and dynein–dynactin, and loss of HookA significantly weakens dynein–early endosome interaction, causing a virtually complete absence of early endosome movement. Thus, HookA is a novel linker important for dynein–early endosome interaction in vivo.
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