Docosahexaenoic fatty acid-containing phospholipids affect plasma membrane susceptibility to disruption by bacterial toxin-induced macroapertures

Meng-Chen Tsai (1, 2) , Lucile Fleuriot (1) , Sébastien Janel (3) , David Gonzalez-Rodriguez (4) , Camille Morel (2, 5) , Amel Mettouchi (2, 5) , Delphine Debayle (1) , Stéphane Dallongeville (6) , Jean-Christophe Olivo-Marin (6) , Bruno Antonny (1) , Frank Lafont (4) , Emmanuel Lemichez (2) , Hélène Barelli (1)

1 IPMC - Institut de pharmacologie moléculaire et cellulaire
2 Toxines bactériennes - Bacterial Toxins
3 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
4 LCP-A2MC - Laboratoire de Chimie et Physique - Approche Multi-échelle des Milieux Complexes
5 Université Paris Diderot, Sorbonne Paris Cité, Paris, France
6 BIA - Analyse d'images biologiques - Biological Image Analysis

Metabolic studies and animal knockout models point to the critical role of polyunsaturated docosahexaenoic acid (22:6, DHA)-containing phospholipids (PLs) in physiology. Here, we study the impact of DHA-PLs on the dynamics of transendothelial cell macroapertures (TEMs) tunnels triggered by the RhoA GTPase inhibitory exotoxin C3 from Clostridium botulinum . Through lipidomic analyses, we show that primary human umbilical vein endothelial cells (HUVECs) subjected to DHA-diet undergo a 6-fold DHA-PLs enrichment in plasma membrane at the expense of monounsaturated OA-PLs. In contrast, OA-diet had almost no effect on PLs composition. Consequently, DHA treatment increases the nucleation rate of TEMs by 2-fold that we ascribe to a reduction of cell thickness. We reveal that the global transcellular area of cells remains conserved through a reduction of the width and lifetime of TEMs. Altogether, we reveal a homeostasis between plasma membrane DHA-PLs content and large-scale membrane dynamics.

Domains: Life Sciences [q-bio]; Microbiology and Parasitology; Cellular Biology

Meng-Chen Tsai, Lucile Fleuriot, Sébastien Janel, David Gonzalez-Rodriguez, Camille Morel, et al.. Docosahexaenoic fatty acid-containing phospholipids affect plasma membrane susceptibility to disruption by bacterial toxin-induced macroapertures. 2021. ⟨pasteur-03133140⟩