1. Biochemistry and Chemical Biology
  2. Cell Biology
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Down-regulation of TORC2-Ypk1 signaling promotes MAPK-independent survival under hyperosmotic stress

  1. Alexander Muir
  2. Françoise M Roelants
  3. Garrett Timmons
  4. Kristin L Leskoske
  5. Jeremy Thorner  Is a corresponding author
  1. Massachusetts Institute of Technology, United Kingdom
  2. University of California, Berkeley, United States
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Cite this article as: eLife 2015;4:e09336 doi: 10.7554/eLife.09336

Abstract

In eukaryotes, exposure to hypertonic conditions activates a MAPK (Hog1 in S.cerevisiae and ortholog p38 in human cells). In yeast, intracellular glycerol accumulates to counterbalance the high external osmolarity. To prevent glycerol efflux, Hog1 action impedes the function of the aquaglyceroporin Fps1, in part, by displacing channel co-activators (Rgc1/2). However, Fps1 closes upon hyperosmotic shock even in hog1∆ cells, indicating another mechanism to prevent Fps1-mediated glycerol efflux. In our prior proteome-wide screen, Fps1 was identified as a target of TORC2-dependent protein kinase Ypk1 (Muir et al., 2014). We show here that Fps1 is an authentic Ypk1 substrate and that the open channel state of Fps1 requires phosphorylation by Ypk1. Moreover, hyperosmotic conditions block TORC2-dependent Ypk1-mediated Fps1 phosphorylation, causing channel closure, glycerol accumulation, and enhanced survival under hyperosmotic stress. These events are all Hog1-independent. Our findings define the underlying molecular basis of a new mechanism for responding to hypertonic conditions.

Article and author information

Author details

  1. Alexander Muir

    Vander Heiden Lab, Department of Biology and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Françoise M Roelants

    Division of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Garrett Timmons

    Department of Chemistry, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Kristin L Leskoske

    Division of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jeremy Thorner

    Division of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    For correspondence
    jthorner@berkeley.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Tony Hunter, Salk Institute, United States

Publication history

  1. Received: June 10, 2015
  2. Accepted: August 13, 2015
  3. Accepted Manuscript published: August 14, 2015 (version 1)
  4. Version of Record published: August 28, 2015 (version 2)

Copyright

© 2015, Muir et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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