Mammalian VPS45 orchestrates trafficking through the endosomal system

Abstract Vacuolar protein sorting 45 homolog (VPS45), a member of the Sec1/Munc18 (SM) family, has been implicated in regulation endosomal trafficking. VPS45 deficiency human patients results congenital neutropenia, bone marrow fibrosis, and extramedullary renal hematopoiesis. Detailed mechanisms function are unknown. Here, we show an essential role mammalian maintaining intracellular organization endolysosomal vesicles promoting recycling cell-surface receptors. Loss causes defective Rab5-to-Rab7 conversion resulting trapping cargos early endosomes impaired delivery to lysosomes. In this context, demonstrate aberrant trafficking granulocyte colony-stimulating factor receptor absence VPS45. Furthermore, find that lack mice is not compatible with embryonic development. Thus, identify as critical regulator through system embryogenesis mice.