biostudies-literatureNorris AAresty Research CenterNIHNIGMS NIH HHSe1010296https://www.ebi.ac.uk/biostudies/studies/S-EPMC9642905biostudies-literatureUnknown18(10)After endocytosis, transmembrane cargo is differentially sorted into degradative or recycling pathways. This process is facilitated by recruitment into physically distinct degradative or recycling microdomains on the limiting membrane of individual endosomes. Endosomal sorting complexes required for transport (ESCRT) mark the degradative microdomain, while the recycling domain is marked by the retromer complex and associated proteins RME-8 and SNX-1. The separation of endosomal microdomains is also controlled by RME-8 and SNX-1, at least in part via removal of degradative component HRS/HGRS-1 from the recycling microdomain. This activity is likely due to recruitment and activation of chaperone Hsc70 on the endosome by the RME-8 DNAJ domain. To better understand the mechanism of RME-8 functPLoS geneticsMutagenesis and structural modeling implicate RME-8 IWN domains as conformational control points.PMC96429055R01GM135326R01 GM135326McManus CTYing RNorris AGrant BDWang SfalseMutagenesis and structural modeling implicate RME-8 IWN domains as conformational control points.After endocytosis, transmembrane cargo is differentially sorted into degradative or recycling pathways. This process is facilitated by recruitment into physically distinct degradative or recycling microdomains on the limiting membrane of individual endosomes. Endosomal sorting complexes required for transport (ESCRT) mark the degradative microdomain, while the recycling domain is marked by the retromer complex and associated proteins RME-8 and SNX-1. The separation of endosomal microdomains is also controlled by RME-8 and SNX-1, at least in part via removal of degradative component HRS/HGRS-1 from the recycling microdomain. This activity is likely due to recruitment and activation of chaperone Hsc70 on the endosome by the RME-8 DNAJ domain. To better understand the mechanism of RME-8 funct2022-01-01T00:00:00Z2022 Oct2026-05-27T23:07:11.148Z2024-12-04T08:02:19.52ZS-EPMC96429053627930810.1371/journal.pgen.1010296