Rab5 Proteins Regulate Activation and Localization of Target of Rapamycin Complex 1

The mechanistic target of rapamycin (mTOR) complex 1 is regulated by small GTPase activators and localization signals. We examine here the role of the small GTPase Rab5 in the localization and activation of TORC1 in yeast and mammalian cells. Rab5 mutants disrupt mTORC1 activation and localization in mammalian cells, whereas disruption of the Rab5 homolog in yeast, Vps21, leads to decreased TORC1 function. Additionally, regulation of PI(3)P synthesis by Rab5 and Vps21 is essential for TORC1 function in both contexts.