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DHA-containing phospholipids control membrane fusion and transcellular tunnel dynamics

Abstract : 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.
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Submitted on : Wednesday, August 3, 2022 - 2:41:25 PM
Last modification on : Thursday, September 22, 2022 - 6:42:05 PM


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Meng-Chen Tsai, Lucile Fleuriot, Sébastien Janel, David Gonzalez-Rodriguez, Camille Morel, et al.. DHA-containing phospholipids control membrane fusion and transcellular tunnel dynamics. Journal of Cell Science, Company of Biologists, 2022, 135 (5), pp.jcs259119. ⟨10.1242/jcs.259119⟩. ⟨pasteur-03744949⟩



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