Regulation of endosomal clathrin and retromer-mediated endosome to Golgi retrograde transport by the J-domain protein RME-8

Abstract

After endocytosis, most cargo enters the pleiomorphic early endosomes in which sorting occurs. As endosomes mature, transmembrane cargo can be sequestered into inwardly budding vesicles for degradation, or can exit the endosome in membrane tubules for recycling to the plasma membrane, the recycling endosome, or the Golgi apparatus. Endosome to Golgi transport requires the retromer complex. Without retromer, recycling cargo such as the MIG‐14/Wntless protein aberrantly enters the degradative pathway and is depleted from the Golgi. Endosome‐associated clathrin also affects the recycling of retrograde cargo and has been shown to function in the formation of endosomal subdomains. Here, we find that the Caemorhabditis elegans endosomal J‐domain protein RME‐8 associates with the retromer component SNX‐1. Loss of SNX‐1, RME‐8, or the clathrin chaperone Hsc70/HSP‐1 leads to over‐accumulation of endosomal clathrin, reduced clathrin dynamics, and missorting of MIG‐14 to the lysosome. Our results indicate a mechanism, whereby retromer can regulate endosomal clathrin dynamics through RME‐8 and Hsc70, promoting the sorting of recycling cargo into the retrograde pathway.

A TOCA/CDC-42/PAR/WAVE functional module required for retrograde endocytic recycling

“…This leads to increased MIG-14 degradation and reduced steady-state levels of the MIG-14 protein (12)(13)(14). Consistent with the idea that loss of the TOCA proteins also leads to missorting of MIG-14 into the degradative pathway, we found that more MIG-14-GFP colocalized with late endosome and lysosome marker tag RFP-RAB-7 in toca double mutant animals than in WT animals (SI Appendix, Fig.…”

“…hTfR and hTAC recycle to the plasma membrane via recycling endosomes, also known as the endocytic recycling compartment (4,7). MIG-14 recycles to the TGN, but previous work had not tested whether MIG-14 transits the recycling endosome en route to the Golgi (12)(13)(14).…”

RAB-10-GTPase–mediated regulation of endosomal phosphatidylinositol-4,5-bisphosphate

“…Although it has been suggested that the budding of clathrincoated vesicles contributes to endocytic recycling, a flat clathrin lattice on endosomes has been suggested to create and/or maintain degradative subdomains on endosomes associated with HRS and ESCRT proteins, regulating the sorting of ubiquitinated cargo proteins in the endosome (44)(45)(46). Thus, another possibility is that ACAPs could interact with clathrin in the flat lattice to affect the balance in degradation and recycling that must be maintained in the endosomal system.…”

SEC-10 and RAB-10 coordinate basolateral recycling of clathrin-independent cargo through endosomal tubules in Caenorhabditis elegans

“…S6 B and C) as hTAC-positive tubular structures. As a comparison, localization of MIG-14, another endogenous CDE cargo (42)(43)(44), was confined to vesicular structures and was not altered in sec-10 mutants (Fig. S6 B and D).…”