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Membrane lipid poly-unsaturation selectively affects dopamine D2 receptor endocytosis.

Overview

Authors: Silvia Sposini1,2, Rim Baccouch3, Mathias Lescuyer4, Aditi A Mali1, Véronique De Smedt-Peyrusse5, Joyce Heuninck4, Ana Gorse3, Thierry Durroux4, Pierre Trifilieff5, David Perrais1, Isabel Alves3
ORCID iDs: Silvia Sposini, Rim Baccouch, Aditi A Mali, David Perrais, Isabel Alves
  1. IINS, Université de Bordeaux, CNRS UMR 5297, Bordeaux, France
  2. IRDB, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
  3. CBMN, Université de Bordeaux, CNRS UMR 5248, Pessac, France
  4. IGF, Université de Montpellier, CNRS, INSERM, Montpellier, France
  5. Université de Bordeaux, INRAE, Bordeaux INP, NutriNeuro, Bordeaux, France
Institutions: Centre National de la Recherche Scientifique (France); Université de Bordeaux (France); Institut Interdisciplinaire de Neuroscience (France); Imperial College London (United Kingdom); Chimie et Biologie des Membranes et des Nanoobjects (France); Inserm (France); Université de Montpellier (France); Institut de Génomique Fonctionnelle (France); Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (France); NutriNeuro (France); Institut Polytechnique de Bordeaux (France)
Journal: Nature communications, volume 17, issue 1, article 6661
Dates: received 11 February 2025; accepted 28 April 2026; published online 20 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41467-026-73057-5 · PMID 42161905 · PMCID PMC13381900 · OpenAlex W7161795095
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: human (organism), cellular / molecular (subfield)
Methods: Statistics, Evoked potentials
Keywords: Endocytosis, Cellular neuroscience, Membrane lipids, G protein-coupled receptors, Membrane structure and assembly
MeSH: Endocytosis*, Fatty Acids, Unsaturated*, Membrane Lipids*, Receptors, Dopamine D2*, Animals, beta-Arrestin 2, Cell Membrane, HEK293 Cells, Humans, Neurons, Protein Transport (* major topic)
Topic: Cellular transport and secretion (Cell Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Wellcome Trust (218650/Z/19/Z); Agence Nationale de la Recherche (French National Research Agency) (ANR-20-CE14-0020, ANR-19-CE16-0003, ANR-21-CE44-0019, ANR-14-CE16-0012)
Citations: not cited yet (Europe PMC); 85 references in the paper

Abstract

The brain is highly enriched in poly-unsaturated fatty acids (PUFAs) and their deficiency has been associated with several neuropsychiatric disorders. Here, we demonstrate that the Dopamine receptor D2 (D2R), a class A G protein coupled receptor (GPCR) which is a main target of antipsychotics, displays specific sensitivity to membrane PUFA composition. We found that membrane enrichment with either of two distinct PUFAs significantly impairs agonist-induced D2R endocytosis in HEK-293 cells and cortical neurons. This treatment does not affect clathrin-mediated endocytosis or the internalization of several other GPCRs. Moreover, we show that D2R clustering at endocytic pits is not affected, but that recruitment of β-arrestin2 is strongly impaired and endocytic vesicle formation is slowed down. Finally, mutation of key residues in intracellular loop 2 abolishes the sensitivity of D2R endocytosis to PUFA enrichment. We conclude that D2R trafficking is specifically dependent on membrane PUFAs, which could influence its role in the control of brain function and behavior.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

Datasets cited

Data availability

The raw data generated in this study have been deposited in the Zenodo database under accession code 19493172 (https://doi.org/10.5281/zenodo.19493172). Source data are provided as a Source data file with this paper. Source data are provided with this paper.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 11 authors, 5 keywords, 11 MeSH terms, 2 funders, 85 references.

Cite

This paper

Sposini, S., Baccouch, R., Lescuyer, M., Mali, A. A., De Smedt-Peyrusse, V., Heuninck, J., Gorse, A., Durroux, T., Trifilieff, P., Perrais, D., & Alves, I. (2026). Membrane lipid poly-unsaturation selectively affects dopamine D2 receptor endocytosis. Nature communications, 17(1), 6661. https://doi.org/10.1038/s41467-026-73057-5

BibTeX

@article{sposini2026membrane,
author = {Sposini, Silvia and Baccouch, Rim and Lescuyer, Mathias and Mali, Aditi A and De Smedt-Peyrusse, Véronique and Heuninck, Joyce and Gorse, Ana and Durroux, Thierry and Trifilieff, Pierre and Perrais, David and Alves, Isabel},
title = {{Membrane lipid poly-unsaturation selectively affects dopamine D2 receptor endocytosis}},
journal = {Nature communications},
year = {2026},
month = may,
volume = {17},
number = {1},
pages = {6661},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/s41467-026-73057-5},
url = {https://doi.org/10.1038/s41467-026-73057-5},
pmid = {42161905},
pmcid = {PMC13381900}
}

RIS

TY - JOUR
AU - Sposini, Silvia
AU - Baccouch, Rim
AU - Lescuyer, Mathias
AU - Mali, Aditi A
AU - De Smedt-Peyrusse, Véronique
AU - Heuninck, Joyce
AU - Gorse, Ana
AU - Durroux, Thierry
AU - Trifilieff, Pierre
AU - Perrais, David
AU - Alves, Isabel
TI - Membrane lipid poly-unsaturation selectively affects dopamine D2 receptor endocytosis
T2 - Nature communications
J2 - Nat Commun
PY - 2026
DA - 2026/05/20
VL - 17
IS - 1
SP - 6661
SN - 2041-1723
PB - Nature Publishing Group
DO - 10.1038/s41467-026-73057-5
UR - https://doi.org/10.1038/s41467-026-73057-5
LA - en
ER -

CSL-JSON

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