The localization of mTORC1 signaling

Abstract

Cells sense and respond to their environment by maintaining appropriate activity levels and localizations of key signaling proteins. In eukaryotic cells, cell size is increasingly appreciated as being coordinated by the Target of Rapamycin (TOR) Pathway. TOR is a serine/threonine kinase that resides in two distinct protein complexes which in mammals are referred to as mTORC1 and mTORC2. While significant emphasis has been placed on defining which pathways TOR controls and on how TOR activity is set, less is known about where TOR is positioned or positions its effectors to control growth. In the work described here, we identify and characterize three distinct aspects of the localization of mTORC1 signaling: the redistribution of the mTORC1 effectors, lipin 1 and SREBP, in controlling sterol- and lipogenesis; mTORC1- mediated regulation of actin-myosin contractility during cytokinesis; the regulation of mTORC1 localization in response to amino acids. Through these studies, we provide not only insights into the topology of cell growth, but also reveal how derangements of these localizations might contribute to conditions such as cancer and metabolic disease.