Membrane lipid poly-unsaturation selectively affects dopamine D2 receptor internalization

Silvia Sposini, Rim Baccouch, Mathias Lescuyer, Aditi A Mali, Véronique De Smedt-Peyrusse, Joyce Heuninck, Ana Gorse, Thierry Durroux, Pierre Trifilieff, David Perrais, Isabel Alves
2023 · doi:10.1101/2023.12.14.571632
preprint OA: gold CC-BY-4.0
📄 Open PDF View at publisher

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 unique 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 uniquely dependent on membrane PUFAs, which could influence its role in the control of brain function and behavior.

My notes (saved in your browser only)

Funding

funders
[{'doi': None, 'name': None, 'awards': ['ANR-21-CE44-0019']}, {'doi': None, 'name': None, 'awards': ['ANR-14-CE16-0012']}, {'doi': None, 'name': None, 'awards': ['ANR-19-CE16-0003']}, {'doi': None, 'name': None, 'awards': ['ANR-20-CE14-002']}, {'doi': '10.13039/501100002915', 'name': 'Fondation pour la Recherche Médicale', 'awards': []}, {'doi': None, 'name': None, 'awards': ['218650/Z/19/Z']}]

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. The paper's references may be in our DB but unresolved to ``paper_id`` (resolution happens at ingest when the cited DOI matches a row we already have). Run the cross-source citation reconcile pass to retry.

References (80)

Source provenance

crossref
last seen: 2026-06-28T06:30:24.563946+00:00
europepmc
last seen: 2026-05-19T01:45:01.086888+00:00
unpaywall
last seen: 2026-05-21T02:00:01.467718+00:00
License: CC-BY-4.0