WDR91 specifies the endosomal retrieval subdomain for retromer-dependent recycling

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.

Automated summary

WDR91 is identified as an important factor in retromer-dependent recycling, promoting the interaction of Rab7 with SNX-retromer components and facilitating the formation of the endosomal retrieval subdomain.