Lipid accumulation controls the balance between surface connection and scission of caveolae

  1. Madlen Hubert
  2. Elin Larsson
  3. Naga Venkata Gayathri Vegesna
  4. Maria Ahnlund
  5. Annika I Johansson
  6. Lindon WK Moodie
  7. Richard Lundmark  Is a corresponding author
  1. Umeå University, Sweden
  2. Swedish University of Agricultural Sciences, Sweden
  3. Uppsala University, Sweden

Abstract

Caveolae are bulb-shaped invaginations of the plasma membrane (PM) that undergo scission and fusion at the cell surface and are enriched in specific lipids. However, the influence of lipid composition on caveolae surface stability is not well described or understood. Accordingly, we inserted specific lipids into the cell PM via membrane fusion and studied their acute effects on caveolae dynamics. We demonstrate that sphingomyelin stabilizes caveolae to the cell surface, while cholesterol and glycosphingolipids drive caveolae scission from the PM. Whilst all three lipids accumulated specifically in caveolae, cholesterol and sphingomyelin were actively sequestered, whereas glycosphingolipids diffused freely. The ATPase EHD2 restricts lipid diffusion and counteracts lipid-induced scission. We propose that specific lipid accumulation in caveolae generates an intrinsically unstable domain prone to scission if not restrained by EHD2 at the caveolae neck. This work provides a mechanistic link between caveolae and their ability to sense the PM lipid composition.

Data availability

All data generated or analysed during this study are included in the manuscript, supporting files and source data files provided for each figure

Article and author information

Author details

  1. Madlen Hubert

    Integrative Medical Biology, Umeå University, Umeå, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  2. Elin Larsson

    Integrative Medical Biology, Umeå University, Umeå, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  3. Naga Venkata Gayathri Vegesna

    Integrative Medical Biology, Umeå University, Umeå, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  4. Maria Ahnlund

    Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  5. Annika I Johansson

    Department of Molecular Biology, Umeå University, Umeå, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  6. Lindon WK Moodie

    Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  7. Richard Lundmark

    Integrative Medical Biology, Umeå University, Umeå, Sweden
    For correspondence
    richard.lundmark@umu.se
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9104-724X

Funding

Vetenskapsrådet (dnr 2017-04028)

  • Richard Lundmark

Cancerfonden (CAN 2017/735)

  • Richard Lundmark

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: January 9, 2020
  2. Accepted: April 29, 2020
  3. Accepted Manuscript published: May 4, 2020 (version 1)
  4. Version of Record published: May 20, 2020 (version 2)

Copyright

© 2020, Hubert 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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  1. Madlen Hubert
  2. Elin Larsson
  3. Naga Venkata Gayathri Vegesna
  4. Maria Ahnlund
  5. Annika I Johansson
  6. Lindon WK Moodie
  7. Richard Lundmark
(2020)
Lipid accumulation controls the balance between surface connection and scission of caveolae
eLife 9:e55038.
https://doi.org/10.7554/eLife.55038

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