Towards a molecular understanding of endosomal trafficking by Retromer and Retriever

• Published in: Traffic (Copenhagen, Denmark) Vol. 20; no. 7; pp. 465 - 478
• Main Authors: Chen, Kai‐En, Healy, Michael D., Collins, Brett M.
• Format: Journal Article
• Language: English
• Published: Former Munksgaard John Wiley & Sons A/S 01.07.2019; Wiley Subscription Services, Inc
• Subjects: Adaptor proteins; C16orf62; CCC; CCDC22; CCDC93; Commander; COMMD; Cooperativity; DSCR3; endosome; Endosomes; Golgi apparatus; Integrins; Lipoprotein receptors; Membrane proteins; Nexin; Retriever; Retromer; sorting nexin; Vps26; Vps29; Vps35; WASH complex; C16orf62; CCC; Retriever; WASH complex; Commander; sorting nexin; Vps35; COMMD; Vps26; Vps29; DSCR3; endosome; CCDC22; CCDC93; Retromer
• ISSN: 1398-9219; 1600-0854
• DOI: 10.1111/tra.12649

Endosomes are dynamic intracellular compartments that control the sorting of a constant stream of different transmembrane cargos either for ESCRT‐mediated degradation or for egress and recycling to compartments such as the Golgi and the plasma membrane. The recycling of cargos occurs within tubulovesicular membrane domains and is facilitated by peripheral membrane protein machineries that control both membrane remodelling and selection of specific transmembrane cargos. One of the primary sorting machineries is the Retromer complex, which controls the recycling of a large array of different cargo molecules in cooperation with various sorting nexin (SNX) adaptor proteins. Recently a Retromer‐like complex was also identified that controls plasma membrane recycling of cargos including integrins and lipoprotein receptors. Termed “Retriever,” this complex uses a different SNX family member SNX17 for cargo recognition, and cooperates with the COMMD/CCDC93/CCDC22 (CCC) complex to form a larger assembly called “Commander” to mediate endosomal trafficking. In this review we focus on recent advances that have begun to provide a molecular understanding of these two distantly related transport machineries. The Retromer and Retriever complexes are structurally related protein assemblies that both play major roles in the sorting of transmembrane cargo proteins through endosomal compartments. This review highlights recent advances in our understanding of the molecular structures of these complexes and their known regulatory interactions, as well as the similarities and differences in their functions in endosomal trafficking.