title: Target of rapamycin signaling mediates vacuolar fission caused by endoplasmic reticulum stress in Saccharomyces cerevisiae.
abstract: The yeast vacuole is equivalent to the mammalian lysosome and, in response to diverse physiological and environmental stimuli, undergoes alterations both in size and number. Here we demonstrate that vacuoles fragment in response to stress within the endoplasmic reticulum (ER) caused by chemical or genetic perturbations. We establish that this response does not involve known signaling pathways linked previously to ER stress but instead requires the rapamycin-sensitive TOR Complex 1 (TORC1), a master regulator of cell growth, together with its downstream effectors, Tap42/Sit4 and Sch9. To identify additional factors required for ER stress-induced vacuolar fragmentation, we conducted a high-throughput, genome-wide visual screen for yeast mutants that are refractory to ER stress-induced changes in vacuolar morphology. We identified several genes shown previously to be required for vacuolar fusion and/or fission, validating the utility of this approach. We also identified a number of new components important for fragmentation, including a set of proteins involved in assembly of the V-ATPase. Remarkably, we find that one of these, Vph2, undergoes a change in intracellular localization in response to ER stress and, moreover, in a manner that requires TORC1 activity. Together these results reveal a new role for TORC1 in the regulation of vacuolar behavior.
authors.affiliation: Department of Molecular and Cellular Biology, College of Biological Sciences, University of California, Davis, Davis, CA 95616.
authors.forename: Bobbiejane
authors.initials: B
authors.lastname: Stauffer
authors.affiliation: Department of Molecular and Cellular Biology, College of Biological Sciences, University of California, Davis, Davis, CA 95616 tpowers@ucdavis.edu).
authors.forename: Ted
authors.initials: T
authors.lastname: Powers
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000235:genetics; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014617:Vacuoles / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; C100984:TAP42 protein, S cerevisiae; C561842:TORC1 protein complex, S cerevisiae; D014157:Transcription Factors; C079033:VPH2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C530964:SCH9 protein, S cerevisiae