WDR91 specifies the endosomal retrieval subdomain for retromer-dependent recycling.

WDR91 specifies the endosomal retrieval subdomain for retromer-dependent recycling.
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WDR91 指定了逆转录酶依赖性回收的内体修复子域

DOI:
10.1083/jcb.202203013
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发表时间:
2022-12-05
期刊:
The Journal of cell biology
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其他
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Liu等人将WDR 91确定为依赖于逆转录酶的回收的重要参与者。WDR 91促进Rab 7与SNX-逆转录组分的相互作用,并与FAM 21相互作用,促进内体回收亚结构域的形成。膜受体的逆转录酶依赖性内体再循环需要Rab 7、分选连接蛋白(SNX)逆转录酶和调节内体肌动蛋白组织的因子。目前还不完全清楚这些因子如何合作形成内体亚结构域用于货物回收和再循环。在这里,我们报告说,WDR 91,Rab 7效应,是指定的内体检索子域的关键因素。WDR 91的缺失导致细胞内和细胞表面受体的缺陷再循环。WDR 91通过其PX结构域与SNX相互作用,并与VPS 35相互作用,从而促进它们与Rab 7的相互作用。WDR 91还与WASH亚基FAM 21相互作用。在WDR 91缺陷细胞中,Rab 7、SNX-逆转录聚合物和FAM 21不能定位于内体亚结构域,并且内体肌动蛋白组织受损。WDR 91的再表达使得Rab 7、SNX-逆转录聚合物和FAM 21能够集中在WDR 91特异性内体亚结构域,其中逆转录聚合物介导的膜微管化和释放发生。因此,WDR 91协调Rab 7与SNX-逆转录酶和WASH,以建立逆转录酶介导的内体再循环所需的内体回收子域。
Liu et al. identify WDR91 as an important player in retromer-dependent recycling. WDR91 promotes the interaction of Rab7 with SNX-retromer components and interacts with FAM21, facilitating the formation of the endosomal retrieval subdomain. Retromer-dependent endosomal recycling of membrane receptors requires Rab7, sorting nexin (SNX)-retromer, and factors that regulate endosomal actin organization. It is not fully understood how these factors cooperate to form endosomal subdomains for cargo retrieval and recycling. Here, we report that WDR91, a Rab7 effector, is the key factor that specifies the endosomal retrieval subdomain. Loss of WDR91 causes defective recycling of both intracellular and cell surface receptors. WDR91 interacts with SNXs through their PX domain, and with VPS35, thus promoting their interaction with Rab7. WDR91 also interacts with the WASH subunit FAM21. In WDR91-deficient cells, Rab7, SNX-retromer, and FAM21 fail to localize to endosomal subdomains, and endosomal actin organization is impaired. Re-expression of WDR91 enables Rab7, SNX-retromer, and FAM21 to concentrate at WDR91-specific endosomal subdomains, where retromer-mediated membrane tubulation and release occur. Thus, WDR91 coordinates Rab7 with SNX-retromer and WASH to establish the endosomal retrieval subdomains required for retromer-mediated endosomal recycling.
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