Phosphoinositide switches in endocytosis and in the endolysosomal system

Abstract

Phosphoinositides (PIs) and their spatiotemporally controlled production, turnover, and interconversion is catalyzed by specific PI phosphatases and kinases and their regulators to allow rapid switching of subcompartmental PI identity. Recent studies have begun to decipher such PI switches at the molecular level and to unravel their physiological functions in endocytosis and endolysosomal membrane dynamics as well as in the control of autophagy and nutrient signaling at late endosomes/lysosomes. In this review, we summarize recent conceptual progress in the field and outline remaining perspectives and challenges for future research. As dysfunctional PI switches underlie a growing number of developmental disturbances and diseases, understanding how PI switches control endocytosis and endolysosomal function may serve to delineate new avenues for potential drug-based therapies to combat these disorders.