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Lipid accumulation controls the balance between surface connection and scission of caveolae
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
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2020 (English)In: eLIFE, E-ISSN 2050-084X, Vol. 9, article id e55038Article in journal (Refereed) Published
Abstract [en]

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, whereas cholesterol and glycosphingolipids drive caveolae scission from the PM. Although 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.

Place, publisher, year, edition, pages
eLife Sciences Publications Ltd , 2020. Vol. 9, article id e55038
National Category
Biochemistry and Molecular Biology Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-172503DOI: 10.7554/eLife.55038ISI: 000537207600001PubMedID: 32364496Scopus ID: 2-s2.0-85084964804OAI: oai:DiVA.org:umu-172503DiVA, id: diva2:1451386
Funder
Swedish Research Council, 2017-04028Swedish Cancer Society, CAN 2017/735Swedish Cancer Society, CAN2014/746The Kempe FoundationsAvailable from: 2020-07-02 Created: 2020-07-02 Last updated: 2020-07-02Bibliographically approved

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Hubert, MadlenLarsson, ElinVegesna, Naga Venkata GayathriJohansson, Annika I.Moodie, Lindon W. K.Lundmark, Richard

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Hubert, MadlenLarsson, ElinVegesna, Naga Venkata GayathriJohansson, Annika I.Moodie, Lindon W. K.Lundmark, Richard
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Department of Integrative Medical Biology (IMB)Department of Molecular Biology (Faculty of Science and Technology)Department of Chemistry
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Biochemistry and Molecular BiologyCell and Molecular Biology

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