TORC2 Affects Endocytosis through Plasma Membrane Tension

Abstract

Target Of Rapamycin complex 2 (TORC2) is a conserved protein kinase that regulates multiple plasma membrane (PM)-related processes including endocytosis. Direct, chemical inhibition of TORC2 arrests endocytosis but with kinetics that are relatively slow and therefore inconsistent with signaling being mediated solely through simple phosphorylation cascades. Here, we show that, in addition to regulation of the phosphorylation of endocytic proteins, TORC2 also controls endocytosis by modulating PM tension. Elevated PM tension, upon TORC2 inhibition, impinges on endocytosis at two different levels: first, by severing the bonds between the PM adaptor proteins Sla2 and Ent1 and the actin cytoskeleton; and, second, by hindering recruitment of Rvs167, an N-BAR-containing protein important for vesicle fission, to endocytosis sites. These results underline the importance of biophysical cues in the regulation of cellular and molecular processes.