title: The TOR complex 1 is a direct target of Rho1 GTPase.
abstract: The TOR complex 1 (TORC1) in yeast is regulated by various stress conditions. However, the underlying mechanism is poorly understood. In this study, we show that stresses affect TORC1 function through Rho1, a member of Rho family GTPases. Upon activation by stresses, Rho1 binds directly to Kog1, a unique component of TORC1, resulting in downregulation of TORC1 activity and disruption of its membrane association. The binding also triggers the release and activation of the Tap42-2A phosphatase, a major effector of TORC1 that resides on the complex. Rapamycin and caffeine also induce Rho1 activation. While the two agents inhibit TOR directly, their effects on TORC1 signaling are largely dependent on Rho1 activation. Our findings demonstrate that TORC1 acts both upstream and downstream of Rho1 GTPase, unveiling a mechanism that integrates stress and nutrient signals to coordinate Rho1-mediated spatial expansion and TORC1-dependent mass increase.
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Gonghong
authors.initials: G
authors.lastname: Yan
authors.forename: Yumei
authors.initials: Y
authors.lastname: Lai
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D013312:Stress, Physiological; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C515118:Kog1 protein, S cerevisiae; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; C100984:TAP42 protein, S cerevisiae; C561842:TORC1 protein complex, S cerevisiae; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; C530964:SCH9 protein, S cerevisiae; C051302:RHO1 protein, S cerevisiae; D020741:rho GTP-Binding Proteins; D020123:Sirolimus