WDR91 is a Rab7 effector required for neuronal development.

ABSTRACT: Early-to-late endosome conversion, which is essential for delivery of endosomal cargoes to lysosomes, requires switching of early endosome-specific Rab5 and PtdIns3P to late endosome-specific Rab7 and PtdIns(3,5)P₂ In this study, we identify the WD40-repeat protein WDR91 as a Rab7 effector that couples Rab switching with PtdIns3P down-regulation on endosomes. Loss of WDR91 greatly increases endosomal PtdIns3P levels, arresting endosomes at an intermediate stage and blocking endosomal-lysosomal trafficking. WDR91 is recruited to endosomes by interacting with active guanosine triphosophate-Rab7 and inhibits Rab7-associated phosphatidylinositol 3-kinase activity. In mice, global Wdr91 knockout causes neonatal death, whereas brain-specific Wdr91 inactivation impairs br

SUBMITTER: Liu K 

PROVIDER: S-EPMC5626554 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature