1. Biochemistry and Chemical Biology
  2. Cell Biology
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TORC2-dependent protein kinase Ypk1 phosphorylates ceramide synthase to stimulate synthesis of complex sphingolipids

  1. Alexander Muir
  2. Subramaniam Ramachandran
  3. Françoise M Roelants
  4. Garrett Timmons
  5. Jeremy Thorner  Is a corresponding author
  1. University of California, Berkeley, United States
Research Article
  • Cited 69
  • Views 3,368
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Cite this article as: eLife 2014;3:e03779 doi: 10.7554/eLife.03779

Abstract

Plasma membrane lipid composition must be maintained during growth and under environmental insult. In yeast, signaling mediated by TOR Complex 2 (TORC2)-dependent protein kinase Ypk1 controls lipid abundance and distribution in response to membrane stress. Ypk1, among other actions, alleviates negative regulation of L-serine:palmitoyl-CoA acyltransferase, upregulating production of long-chain base precursors to sphingolipids. To explore other roles for TORC2-Ypk1 signaling in membrane homeostasis, we devised a three-tiered genome-wide screen to identify additional Ypk1 substrates, which pinpointed both catalytic subunits of the ceramide synthase complex. Ypk1-dependent phosphorylation of both proteins increased upon either sphingolipid depletion or heat shock and was important for cell survival. Sphingolipidomics, other biochemical measurements and genetic analysis demonstrated that these modifications of ceramide synthase increased its specific activity and stimulated channeling of long-chain base precursors into sphingolipid end-products. Control at this branch point also prevents accumulation of intermediates that could compromise cell growth by stimulating autophagy.

Article and author information

Author details

  1. Alexander Muir

    University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Subramaniam Ramachandran

    University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Françoise M Roelants

    University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Garrett Timmons

    University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jeremy Thorner

    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 25, 2014
  2. Accepted: October 2, 2014
  3. Accepted Manuscript published: October 3, 2014 (version 1)
  4. Version of Record published: November 3, 2014 (version 2)

Copyright

© 2014, 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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