DHA-containing phospholipids control membrane fusion and transcellular tunnel dynamics
- Others:
- Institut de pharmacologie moléculaire et cellulaire (IPMC) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
- Toxines bactériennes - Bacterial Toxins ; Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
- Centre d'Infection et d'Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL) ; Institut Pasteur de Lille ; Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)
- Laboratoire de Chimie et Physique - Approche Multi-échelle des Milieux Complexes (LCP-A2MC) ; Université de Lorraine (UL)
- Analyse d'images biologiques - Biological Image Analysis (BIA) ; Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
- This work was supported by a grant from the Fondation pour la Recherche Médicale (Convention DEQ20180339156 Equipes FRM 2018), the Agence Nationale de la Recherche (ANR-11-LABX-0028-01, ANR-15-CE18-0016, ANR 10-EQPX-04-01, ANR-10-INBS-04 and ANR-10-LABX-62-IBEID) and FEDER 12001407, and partially by grants from the France-BioImaging infrastructure (ANR-10-INBS-04) and the Labex IBEID (ANR-10-LABX-62-IBEID). M.-C.T. was supported by a PhD fellowship from the Labex Signalife PhD Programme and by the Fondation pour la Recherche Médicale (Contrat FDT201904008135).
- ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011)
- ANR-15-CE18-0016,TransEndotheliaTunnel,Vers la prévention de dysfonctions vasculaires et la délivrance de médicaments au travers des endothelia(2015)
- ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
- ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010)
Description
Metabolic studies and animal knockout models point to the critical role of polyunsaturated docosahexaenoic acid (22:6, DHA)-containing phospholipids (DHA-PLs) in physiology. Here, we investigated the impact of DHA-PLs on the dynamics of transendothelial cell macroapertures (TEMs) triggered by RhoA inhibition-associated cell spreading. Lipidomic analyses showed that human umbilical vein endothelial cells (HUVECs) subjected to a DHA diet undergo a 6-fold enrichment in DHA-PLs at the plasma membrane (PM) at the expense of monounsaturated oleic acid-containing PLs (OA-PLs). Consequently, DHA-PL enrichment at the PM induces a reduction in cell thickness and shifts cellular membranes towards a permissive mode of membrane fusion for transcellular tunnel initiation. We provide evidence that a global homeostatic control of membrane tension and cell cortex rigidity minimizes overall changes of TEM area through a decrease of TEM size and lifetime. Conversely, low DHA-PL levels at the PM lead to the opening of unstable and wider TEMs. Together, this provides evidence that variations of DHA-PL levels in membranes affect cell biomechanical properties.
Abstract
International audience
Additional details
- URL
- https://hal-pasteur.archives-ouvertes.fr/pasteur-03744949
- URN
- urn:oai:HAL:pasteur-03744949v1
- Origin repository
- UNICA