PTEN reduces endosomal PtdIns(4,5)P₂ in a phosphatase-independent manner via a PLC pathway.

ABSTRACT: The tumor suppressor PTEN dephosphorylates PtdIns(3,4,5)P₃ into PtdIns(4,5)P₂ Here, we make the unexpected discovery that in Drosophila melanogaster PTEN reduces PtdIns(4,5)P₂ levels on endosomes, independently of its phosphatase activity. This new PTEN function requires the enzymatic action of dPLCXD, an atypical phospholipase C. Importantly, we discovered that this novel PTEN/dPLCXD pathway can compensate for depletion of dOCRL, a PtdIns(4,5)P₂ phosphatase. Mutation of OCRL1, the human orthologue of dOCRL, causes oculocerebrorenal Lowe syndrome, a rare multisystemic genetic disease. Both OCRL1 and dOCRL loss have been shown to promote accumulation of PtdIns(4,5)P₂ on endosomes and cytokinesis defects. Here, we show that PTEN o

SUBMITTER: Mondin VE 

PROVIDER: S-EPMC6605811 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature