A PX-BAR protein Mvp1/SNX8 and a dynamin-like GTPase Vps1 drive endosomal recycling

Abstract

Membrane protein recycling systems are essential for maintenance of the endosome-lysosome system. In yeast, retromer and Snx4 coat complexes are recruited to the endosomal surface where they recognize cargos. They sort cargo and deform the membrane into recycling tubules that bud from the endosome and target to the Golgi. Here, we reveal that the SNX-BAR protein, Mvp1, mediates an endosomal recycling pathway which is mechanistically distinct from the retromer and Snx4 pathways. Mvp1 deforms the endosomal membrane and sorts cargos containing a specific sorting motif into a membrane tubule. Subsequently, Mvp1 recruits the dynamin-like GTPase Vps1 to catalyze membrane scission and release of the recycling tubule. Similarly, SNX8, the human homolog of Mvp1, which has been also implicated in Alzheimers disease, mediates formation of an endosomal recycling tubule. Thus, we present evidence for a novel endosomal retrieval pathway that is conserved from yeast to humans. In BriefPX-BAR Mvp1 and dynamin-like GTPase Vps1 drive retromer independent endosomal recycling. HighlightsO_LIRetromer- and Snx4-independent endosomal recycling pathway discovered C_LIO_LISNX-BAR Mvp1 and dynamin-like GTPase Vps1 mediate cargo sorting into recycling tubules/vesicles in the absence of retromer function C_LIO_LIMvp1 together with retromer and Snx4 complexes contribute to proper endosome function C_LIO_LIMvp1 mediated recycling is evolutionary conserved from yeast to humans C_LIO_LICharacters: 43,934/45,000 (including spaces and main figure legends but excluding STAR Methods text, supplemental item legends, and References section) C_LI