RRAG GTPases link nutrient availability to gene expression, autophagy and lysosomal biogenesis

Abstract

When the levels of intracellular amino acids are high, RRAG GTPases recruit MTORC1 to lysosomes and promote its activation. We found that RRAGs also recruit specific MTORC1 substrates to the lysosomal surface, thus facilitating MTORC1-mediated phosphorylation and regulation. In particular, active RRAGs interact with the transcription factor EB (TFEB), the master regulator of a gene network that promotes lysosomal biogenesis and autophagy. Redistribution to lysosomes is critical for MTORC1-dependent inactivation of TFEB under nutrient-rich conditions. Therefore, RRAGs play a critical role coordinating nutrient availability and cellular clearance. © 2013 Landes Bioscience.