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

First Author  Liu N Year  2022
Journal  J Cell Biol Volume  221
Issue  12 PubMed ID  36190447
Mgi Jnum  J:353316 Mgi Id  MGI:7461022
Doi  10.1083/jcb.202203013 Citation  Liu N, et al. (2022) WDR91 specifies the endosomal retrieval subdomain for retromer-dependent recycling. J Cell Biol 221(12)
abstractText  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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