A FAM21-containing WASH complex regulates retromer-dependent sorting.

A FAM21-containing WASH complex regulates retromer-dependent sorting.
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DOI:
10.1016/j.devcel.2009.09.009
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发表时间:
2009-11
期刊:
影响因子:
11.8
通讯作者:
Billadeau, Daniel D.
Billadeau, Daniel D.
中科院分区:
生物学1区
文献类型:
--
作者:
Gomez, Timothy S.;Billadeau, Daniel D.

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Arp 2/3复合物调节内吞作用、分选和运输,然而Arp 2/3刺激因子协调这些不同的事件仍然不明确。WASH(Wiskott-Aldrich Syndrome Protein and SCAR Homolog)是一种Arp 2/3激活剂,功能未知,在灵长类进化过程中被复制。我们证明,WASH协会与微管蛋白和本地化的早期内体亚结构域,这是丰富的Arp 2/3,F-肌动蛋白,和retromer组件。虽然WASH定位于活化受体,但它对内吞作用不是必需的。然而,WASH确实调节逆转录酶介导的逆行CI-MPR运输,这需要其与内体、Arp 2/3指导的F-肌动蛋白调节和微管蛋白相互作用的关联。此外,WASH存在于含有FAM 21的多蛋白复合物中,FAM 21将WASH连接到内体,并且是WASH依赖性逆转录酶介导的分选所需的。值得注意的是,在没有WASH的情况下,逆转录聚合物微管被夸大,支持WASH将逆转录聚合物介导的含有微管的货物连接到微管以进行高尔基体定向运输并产生用于微管断裂的F-肌动蛋白驱动力的模型。
The Arp2/3 complex regulates endocytosis, sorting and trafficking, yet the Arp2/3-stimulating factors orchestrating these distinct events remain ill-defined. WASH (Wiskott-Aldrich Syndrome Protein and SCAR Homolog) is an Arp2/3 activator with unknown function that was duplicated during primate evolution. We demonstrate that WASH associates with tubulin and localizes to early endosomal subdomains, which are enriched in Arp2/3, F-actin, and retromer components. While WASH localized with activated receptors, it was not essential for endocytosis. However, WASH did regulate retromer-mediated retrograde CI-MPR trafficking, which required its association with endosomes, Arp2/3-directed F-actin regulation and tubulin interaction. Moreover, WASH exists in a multi-protein complex containing FAM21, which links WASH to endosomes and is required for WASH-dependent retromer-mediated sorting. Significantly, without WASH, retromer tubulation was exaggerated supporting a model wherein WASH links retromer-mediated cargo containing tubules to microtubules for Golgi-directed trafficking and generates F-actin-driven force for tubule scission.
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