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PreprintCited by 40Lipid metabolism and biosynthesisCellular transport and secretionLipid Membrane Structure and Behavior

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MOSPD2 a new endoplasmic reticulum-lipid droplet tether functioning in LD homeostasis

Open access
Zouiouich, Mehdi, Di Mattia, Thomas, Martinet, Arthur, Eichler, Julie, Wendling, Corinne, Tomishige, Nario, Grandgirard, Erwan, Fuggetta, Nicolas, Ramain, Catherine, Mizzon, Giulia, Dumesnil, Calvin, Carpentier, Maxime, Reina-San-Martin, Bernardo, Mathelin, Carole, Schwab, Yannick, Thiam, Abdou Rachid, Kobayashi, Toshihide, Drin, Guillaume, Tomasetto, Catherine, Alpy, Fabien·2022·The Journal of Cell Biology
DOI 10.1101/2022.02.11.479928PMC PMC8996327

Preprint — published as 10.1083/jcb.202110044 · Paper page

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Abstract

Membrane contact sites between organelles are organized by protein bridges. Among the components of these contacts, the VAP family comprises endoplasmic reticulum (ER)-anchored proteins, such as MOSPD2, functioning as major ER-organelle tethers. MOSPD2 distinguishes itself from the other members of the VAP family by the presence of a CRAL-TRIO domain. In this study, we show that MOSPD2 forms ER-LD contacts thanks to its CRAL-TRIO domain. MOSPD2 ensures the attachment of the ER to LDs through a direct protein-membrane interaction involving an amphipathic helix that has an affinity for lipid packing defects present at the surface of LDs. Remarkably, the absence of MOSPD2 markedly disturbs the assembly of lipid droplets. These data show that MOSPD2, in addition to being a general ER receptor for inter-organelle contacts, possesses an additional tethering activity and is specifically implicated in the biology of LDs via its CRAL-TRIO domain.

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Metadata

Authors
Zouiouich, M., Di Mattia, T., Martinet, A., Eichler, J., Wendling, C., Tomishige, N., Grandgirard, E., Fuggetta, N., Ramain, C., Mizzon, G., Dumesnil, C., Carpentier, M., Reina-San-Martin, B., Mathelin, C., Schwab, Y., Thiam, A. R., Kobayashi, T., Drin, G., Tomasetto, C., & Alpy, F.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • European Molecular Biology Laboratory (DE)
Corresponding author
  • Tomasetto, Catherine
  • Alpy, Fabien
ORCID
Venue
The Journal of Cell Biology
Publisher
openRxiv
Published
2022-02-11
Volume
221
Issue
6
Pages
e202110044
ISSN
0021-9525 (ISSN-L)
DOI
10.1101/2022.02.11.479928
PMC
PMC8996327
OpenAlex
W4224073523
Cited by
40
References
1
Citations by year
2026: 11 · 2025: 9 · 2024: 8 · 2023: 7 · 2022: 5
FWCI
3.07
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • The Journal of Cell Biology (publishedVersion, other-oa)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by-nc-sa)
Funders
  • European Molecular Biology Laboratory
  • Alliance Nationale pour les Sciences de la Vie et de la Santé
  • Agence Nationale de la Recherche (ANR-10-IDEX-0002, ANR-17-EURE-, ANR-20-SFRI-0012, ANR‐19, ANR-17-EURE-0023, ANR-10-IDEX, ANR-10-LABX-0030, 0014-01, ANR-17, ANR-10-IDEX0002-02, ANR-10, ANR-10-LABX, ANR-21-CE13-0014, ANR-19-CE44-0003)
  • Institut National de la Santé et de la Recherche Médicale (ANR 10 IDEX 0002, ANR-17-EURE-0023, ANR-20-SFRI-0012, ANR-10-IDEX-0002-02, ANR‐10‐LABX‐0030‐INRT)
  • Fondation pour la Recherche Médicale (ANR-10-LABX-0030-INRT, ANR-10-IDEX-0002-02, ANR-10-IDEX-0002)
  • Université de Strasbourg (10-IDEX-0002, ANR-10-LABX-0030, ANR-10-LABX-0030-INRT, ANR-10-IDEX- 0002, ANR-17-EURE-0023, ANR-10-IDEX-0002-02, ITI 2021 2028)
  • Fondation ARC pour la Recherche sur le Cancer (ANR-10-IDEX-0002, ANR-10-LABX-0030-INRT)
  • Ligue Contre le Cancer (ANR-10-IDEX-0002, ANR-10-LABX-0030-INRT)
  • Centre National de la Recherche Scientifique (ANR-10-IDEX-0002-02, ANR-10-IDEX-0002, ANR-10-LABX-0030-INRT, 2021-2028)
  • CHIST-ERA
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Keywords
VAP proteins, endoplasmic reticulum, lipid droplets, membrane contact sites, lipid droplet homeostasis, amphipathic helix, lipid packing defects, protein-membrane interactions
MeSH terms
Endoplasmic Reticulum, Homeostasis, Membrane Proteins, Receptors, Chemokine, Mitochondrial Membranes, Lipid Droplets

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