1. Biochemistry and Chemical Biology
  2. Cell Biology
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Movement of accessible plasma membrane cholesterol by GRAMD1 lipid transfer protein complex

  1. Tomoki Naito
  2. Bilge Ercan
  3. Logesvaran Krshnan
  4. Alexander Triebl
  5. Dylan Hong Zheng Koh
  6. Fan-Yan Wei
  7. Kazuhito Tomizawa
  8. Federico Tesio Torta
  9. Markus R Wenk
  10. Yasunori Saheki  Is a corresponding author
  1. Nanyang Technological University, Singapore
  2. National University of Singapore, Singapore
  3. Kumamoto University, Japan
Research Article
  • Cited 15
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Cite this article as: eLife 2019;8:e51401 doi: 10.7554/eLife.51401

Abstract

Cholesterol is a major structural component of the plasma membrane (PM). The majority of PM cholesterol forms complexes with other PM lipids, making it inaccessible for intracellular transport. Transition of PM cholesterol between accessible and inaccessible pools maintains cellular homeostasis, but how cells monitor PM cholesterol accessibility remains unclear. We show that endoplasmic reticulum (ER)-anchored lipid transfer proteins, the GRAMD1s, sense and transport accessible PM cholesterol to the ER. GRAMD1s bind one another and populate at ER-PM contacts by sensing a transient expansion of the accessible pool of PM cholesterol via GRAM domains and facilitate its transport via StART-like domains. Cells lacking all three GRAMD1s exhibit striking expansion of the accessible pool of PM cholesterol due to less efficient PM to ER transport of accessible cholesterol. Thus, GRAMD1s facilitate movement of accessible PM cholesterol to the ER in order to counteract acute increase of PM cholesterol, activating non-vesicular cholesterol transport.

Article and author information

Author details

  1. Tomoki Naito

    Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  2. Bilge Ercan

    Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  3. Logesvaran Krshnan

    Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  4. Alexander Triebl

    Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8423-8224
  5. Dylan Hong Zheng Koh

    Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  6. Fan-Yan Wei

    Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
    Competing interests
    The authors declare that no competing interests exist.
  7. Kazuhito Tomizawa

    Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
    Competing interests
    The authors declare that no competing interests exist.
  8. Federico Tesio Torta

    Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  9. Markus R Wenk

    Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  10. Yasunori Saheki

    Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
    For correspondence
    yasunori.saheki@ntu.edu.sg
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1229-6668

Funding

Japan Society for the Promotion of Science (17H05065)

  • Yasunori Saheki

Ministry of Education - Singapore (MOE2017-T2-2-001)

  • Yasunori Saheki

Nanyang Technological University (Nanyang Assistant Professorship (NAP))

  • Yasunori Saheki

Nanyang Technological University (Lee Kong Chian School of Medicine startup grant)

  • Yasunori Saheki

National Research Foundation Singapore (NRFI2015-05)

  • Alexander Triebl
  • Federico Tesio Torta
  • Markus R Wenk

National Research Foundation Singapore (NRFSBP-P4)

  • Alexander Triebl
  • Federico Tesio Torta
  • Markus R Wenk

Japan Society for the Promotion of Science (Overseas Research Fellowship)

  • Tomoki Naito

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

Reviewing Editor

  1. Arun Radhakrishnan, University of Texas Southwestern Medical Center, United States

Publication history

  1. Received: August 27, 2019
  2. Accepted: November 13, 2019
  3. Accepted Manuscript published: November 14, 2019 (version 1)
  4. Version of Record published: December 11, 2019 (version 2)

Copyright

© 2019, Naito 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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