1. Cell Biology
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SAC1 degrades its lipid substrate PtdIns4P in the endoplasmic reticulum to maintain a steep chemical gradient with donor membranes

  1. James P Zewe
  2. Rachel C Wills
  3. Sahana Sangappa
  4. Brady D Goulden
  5. Gerald RV Hammond  Is a corresponding author
  1. University of Pittsburgh, United States
Research Article
  • Cited 38
  • Views 2,250
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Cite this article as: eLife 2018;7:e35588 doi: 10.7554/eLife.35588

Abstract

Gradients of PtdIns4P between organelle membranes and the endoplasmic reticulum (ER) are thought to drive counter-transport of other lipids via non-vesicular traffic. This novel pathway requires the SAC1 phosphatase to degrade PtdIns4P in a 'cis' configuration at the ER to maintain the gradient. However, SAC1 has also been proposed to act in 'trans' at membrane contact sites, which could oppose lipid traffic. It is therefore crucial to determine which mode SAC1 uses in living cells. We report that acute inhibition of SAC1 causes accumulation of PtdIns4P in the ER, that SAC1 does not enrich at membrane contact sites, and that SAC1 has little activity in 'trans', unless a linker is added between its ER-anchored and catalytic domains. The data reveal an obligate 'cis' activity of SAC1, supporting its role in non-vesicular lipid traffic and implicating lipid traffic more broadly in inositol lipid homeostasis and function.

Article and author information

Author details

  1. James P Zewe

    Department of Cell Biology, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Rachel C Wills

    Department of Cell Biology, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Sahana Sangappa

    Department of Cell Biology, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Brady D Goulden

    Department of Cell Biology, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Gerald RV Hammond

    Department of Cell Biology, University of Pittsburgh, Pittsburgh, United States
    For correspondence
    ghammond@pitt.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6660-3272

Funding

National Institutes of Health (1R35GM119412-01)

  • James P Zewe
  • Rachel C Wills
  • Sahana Sangappa
  • Brady D Goulden
  • Gerald RV Hammond

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Christopher G Burd, Yale School of Medicine, United States

Publication history

  1. Received: February 1, 2018
  2. Accepted: February 13, 2018
  3. Accepted Manuscript published: February 20, 2018 (version 1)
  4. Version of Record published: February 28, 2018 (version 2)

Copyright

© 2018, Zewe 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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