IpaA reveals distinct modes of vinculin activation during Shigella invasion and cell-matrix adhesion.

Autor:	Cocom-Chan B; Team 'Ca2+ Signaling and Microbial Infections', I2BC, Gif-sur-Yvette, France.; Institut National de la Santé et de la Recherche Médicale U1280, Gif-sur-Yvette, France.; Centre National de la Recherche Scientifique UMR9198, Gif-sur-Yvette, France., Khakzad H; Team 'Ca2+ Signaling and Microbial Infections', I2BC, Gif-sur-Yvette, France.; Institut National de la Santé et de la Recherche Médicale U1280, Gif-sur-Yvette, France.; Centre National de la Recherche Scientifique UMR9198, Gif-sur-Yvette, France.; Université de Lorraine, CNRS, Inria, LORIA, Nancy, France., Konate M; Team 'Ca2+ Signaling and Microbial Infections', I2BC, Gif-sur-Yvette, France.; Institut National de la Santé et de la Recherche Médicale U1280, Gif-sur-Yvette, France.; Centre National de la Recherche Scientifique UMR9198, Gif-sur-Yvette, France., Aguilar DI; Equipe Communication Intercellulaire et Infections Microbiennes, Centre de Recherche Interdisciplinaire en Biologie (CIRB), Collège de France, Paris, France.; Institut National de la Santé et de la Recherche Médicale U1050, Paris, France.; Centre National de la Recherche Scientifique UMR7241, Paris, France.; MEMOLIFE Laboratory of Excellence and Paris Science Lettre, Paris, France., Bello C; Equipe Communication Intercellulaire et Infections Microbiennes, Centre de Recherche Interdisciplinaire en Biologie (CIRB), Collège de France, Paris, France.; Institut National de la Santé et de la Recherche Médicale U1050, Paris, France.; Centre National de la Recherche Scientifique UMR7241, Paris, France.; MEMOLIFE Laboratory of Excellence and Paris Science Lettre, Paris, France., Valencia-Gallardo C; Equipe Communication Intercellulaire et Infections Microbiennes, Centre de Recherche Interdisciplinaire en Biologie (CIRB), Collège de France, Paris, France.; Institut National de la Santé et de la Recherche Médicale U1050, Paris, France.; Centre National de la Recherche Scientifique UMR7241, Paris, France.; MEMOLIFE Laboratory of Excellence and Paris Science Lettre, Paris, France., Zarrouk Y; Team 'Ca2+ Signaling and Microbial Infections', I2BC, Gif-sur-Yvette, France.; Institut National de la Santé et de la Recherche Médicale U1280, Gif-sur-Yvette, France.; Centre National de la Recherche Scientifique UMR9198, Gif-sur-Yvette, France., Fattaccioli J; PASTEUR, Département de Chimie, École Normale Supérieure, PSL University, Sorbonne Université, CNRS, Paris, France.; Institut Pierre-Gilles de Gennes pour la Microfluidique, Paris, France., Mauviel A; Institut Curie, PSL Research University, INSERM U1021, CNRS UMR3347, Team 'TGF-ß and Oncogenesis', Equipe Labellisée LIGUE 2016, Orsay, France.; Université Paris-Sud, Orsay, France.; Centre National de la Recherche Scientifique UMR 3347, Orsay, France., Javelaud D; Institut Curie, PSL Research University, INSERM U1021, CNRS UMR3347, Team 'TGF-ß and Oncogenesis', Equipe Labellisée LIGUE 2016, Orsay, France.; Université Paris-Sud, Orsay, France.; Centre National de la Recherche Scientifique UMR 3347, Orsay, France., Tran Van Nhieu G; Team 'Ca2+ Signaling and Microbial Infections', I2BC, Gif-sur-Yvette, France guy.tranvannhieu@i2bc.paris-saclay.fr.; Institut National de la Santé et de la Recherche Médicale U1280, Gif-sur-Yvette, France.; Centre National de la Recherche Scientifique UMR9198, Gif-sur-Yvette, France.; Equipe Communication Intercellulaire et Infections Microbiennes, Centre de Recherche Interdisciplinaire en Biologie (CIRB), Collège de France, Paris, France.; Institut National de la Santé et de la Recherche Médicale U1050, Paris, France.; Centre National de la Recherche Scientifique UMR7241, Paris, France.; MEMOLIFE Laboratory of Excellence and Paris Science Lettre, Paris, France.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2024 Jun 04; Vol. 7 (8). Date of Electronic Publication: 2024 Jun 04 (Print Publication: 2024).
DOI:	10.26508/lsa.202302418
Abstrakt:	Vinculin is a cytoskeletal linker strengthening cell adhesion. The Shigella IpaA invasion effector binds to vinculin to promote vinculin supra-activation associated with head-domain-mediated oligomerization. Our study investigates the impact of mutations of vinculin D1D2 subdomains' residues predicted to interact with IpaA VBS3. These mutations affected the rate of D1D2 trimer formation with distinct effects on monomer disappearance, consistent with structural modeling of a closed and open D1D2 conformer induced by IpaA. Notably, mutations targeting the closed D1D2 conformer significantly reduced Shigella invasion of host cells as opposed to mutations targeting the open D1D2 conformer and later stages of vinculin head-domain oligomerization. In contrast, all mutations affected the formation of focal adhesions (FAs), supporting the involvement of vinculin supra-activation in this process. Our findings suggest that IpaA-induced vinculin supra-activation primarily reinforces matrix adhesion in infected cells, rather than promoting bacterial invasion. Consistently, shear stress studies pointed to a key role for IpaA-induced vinculin supra-activation in accelerating and strengthening cell-matrix adhesion. (© 2024 Cocom-Chan et al.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu