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Caveolin-1 protects endothelial cells from extensive expansion of transcellular tunnel by stiffening the plasma membrane.
Morel, Camille; Lemerle, Eline; Tsai, Feng-Ching; Obadia, Thomas; Srivastava, Nishit; Marechal, Maud; Salles, Audrey; Albert, Marvin; Stefani, Caroline; Benito, Yvonne; Vandenesch, François; Lamaze, Christophe; Vassilopoulos, Stéphane; Piel, Matthieu; Bassereau, Patricia; Gonzalez-Rodriguez, David; Leduc, Cecile; Lemichez, Emmanuel.
Afiliación
  • Morel C; Institut Pasteur, Université Paris Cité, CNRS UMR6047, Inserm U1306, Unité des Toxines Bactériennes, Département de Microbiologie, Paris, France.
  • Lemerle E; Sorbonne Université, INSERM UMR974, Institut de Myologie, Centre de Recherche en Myologie, Paris, France.
  • Tsai FC; Institut Curie, PSL Research University, CNRS UMR168, Physics of Cells and Cancer Laboratory, Paris, France.
  • Obadia T; Institut Pasteur, Université Paris Cité, Bioinformatics and Biostatistics Hub, Paris, France.
  • Srivastava N; Institut Pasteur, Université Paris Cité, G5 Infectious Diseases Epidemiology and Analytics, Paris, France.
  • Marechal M; Institut Curie and Institut Pierre Gilles de Gennes, PSL Research University, Sorbonne University, Paris, France.
  • Salles A; Institut Pasteur, Université Paris Cité, CNRS UMR6047, Inserm U1306, Unité des Toxines Bactériennes, Département de Microbiologie, Paris, France.
  • Albert M; Institut Pasteur, Université Paris Cité, Photonic Bio-Imaging, Centre de Ressources et Recherches Technologiques (UTechS-PBI, C2RT), Paris, France.
  • Stefani C; Institut Pasteur, Université Paris Cité, Image Analysis Hub, Paris, France.
  • Benito Y; Benaroya Research Institute at Virginia Mason, Department of Immunology, Seattle, United States.
  • Vandenesch F; Centre National de Référence des Staphylocoques, Hospices Civiles de Lyon, Lyon, France.
  • Lamaze C; CIRI, Centre International de Recherche en Infectiologie, Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, ENS de Lyon, Lyon, France, Lyon, France.
  • Vassilopoulos S; Institut Curie, PSL Research University, INSERM U1143, CNRS UMR3666, Membrane Mechanics and Dynamics of Intracellular Signaling Laboratory, Paris, France.
  • Piel M; Sorbonne Université, INSERM UMR974, Institut de Myologie, Centre de Recherche en Myologie, Paris, France.
  • Bassereau P; Institut Curie and Institut Pierre Gilles de Gennes, PSL Research University, Sorbonne University, Paris, France.
  • Gonzalez-Rodriguez D; Institut Curie, PSL Research University, CNRS UMR168, Physics of Cells and Cancer Laboratory, Paris, France.
  • Leduc C; Université de Lorraine, LCP-A2MC, Metz, France.
  • Lemichez E; Université Paris Cité, Institut Jacques Monod, CNRS UMR7592, Paris, France.
Elife ; 122024 Mar 22.
Article en En | MEDLINE | ID: mdl-38517935
ABSTRACT
Large transcellular pores elicited by bacterial mono-ADP-ribosyltransferase (mART) exotoxins inhibiting the small RhoA GTPase compromise the endothelial barrier. Recent advances in biophysical modeling point toward membrane tension and bending rigidity as the minimal set of mechanical parameters determining the nucleation and maximal size of transendothelial cell macroaperture (TEM) tunnels induced by bacterial RhoA-targeting mART exotoxins. We report that cellular depletion of caveolin-1, the membrane-embedded building block of caveolae, and depletion of cavin-1, the master regulator of caveolae invaginations, increase the number of TEMs per cell. The enhanced occurrence of TEM nucleation events correlates with a reduction in cell height due to the increase in cell spreading and decrease in cell volume, which, together with the disruption of RhoA-driven F-actin meshwork, favor membrane apposition for TEM nucleation. Strikingly, caveolin-1 specifically controls the opening speed of TEMs, leading to their dramatic 5.4-fold larger widening. Consistent with the increase in TEM density and width in siCAV1 cells, we record a higher lethality in CAV1 KO mice subjected to a catalytically active mART exotoxin targeting RhoA during staphylococcal bloodstream infection. Combined theoretical modeling with independent biophysical measurements of plasma membrane bending rigidity points toward a specific contribution of caveolin-1 to membrane stiffening in addition to the role of cavin-1/caveolin-1-dependent caveolae in the control of membrane tension homeostasis.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Células Endoteliales / Caveolina 1 Límite: Animals Idioma: En Revista: Elife Año: 2024 Tipo del documento: Article País de afiliación: Francia

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Células Endoteliales / Caveolina 1 Límite: Animals Idioma: En Revista: Elife Año: 2024 Tipo del documento: Article País de afiliación: Francia