Phosphoinositide-based switches in polarized sorting and signaling. Phosphoinositides (PIPs) are critical determinants of cellular polarity that enable the functional segregation of the plasma membrane. PIPs are known to be differentially distributed between distinct membrane domains in polarized cells but their role, in particular that of PI 3-phosphates, in polarized endosomal sorting and signaling remains enigmatic. This project will use advanced optogenetic and chemical biology tools to manipulate PI 3-phosphates “on –demand” in live polarized epithelial cells and in primary neurons. We aim at unraveling general principles as to how PI 3-phosphate-based switches regulate polarized sorting and signaling.