| Title: |
Optineurin links Hace1-dependent Rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division |
| Authors: |
Petracchini, Serena; Hamaoui, Daniel; Doye, Anne; Asnacios, Atef; Fage, Florian; Vitiello, Elisa; Balland, Martial; Janel, Sebastien; Lafont, Frank; Gupta, Mukund; Ladoux, Benoit; Gilleron, Jerôme; Maia, Teresa; Impens, Francis; Gagnoux-Palacios, Laurent; Daugaard, Mads; Sorensen, Poul, H.; Lemichez, Emmanuel; Mettouchi, Amel |
| Contributors: |
Centre méditerranéen de médecine moléculaire (C3M); Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UniCA); Equipe labellisée Ligue contre le Cancer; Matière et Systèmes Complexes (MSC); Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Laboratoire Interdisciplinaire de Physique Saint Martin d’Hères (LIPhy); Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA); Microbiologie cellulaire et physique de l’infection = Cellular Microbiology and Physics of Infection Group Lille (CMPI); Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL); Institut Pasteur de Lille; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS); Institut Jacques Monod (IJM (UMR_7592)); Vlaams Instituut voor Biotechnologie = Flanders Institute for Biotechnology Ghent (VIB); Universiteit Gent = Ghent University = Université de Gand (UGent); Institut de Biologie Valrose (IBV); Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UniCA); Vancouver Prostate Centre Vancouver General Hospital (VPC); Vancouver General Hospital Vancouver, British Columbia, Canada (VGH); University of British Columbia Canada (UBC); Toxines bactériennes - Bacterial Toxins; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047); Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS); This study was supported by institutional INSERM and Institut Pasteur fundings, "Investments for the Future" LabEx SIGNALIFE ANR-11-LABX-0028-01 and grants from the Ligue Nationale contre le Cancer (LNCC labellisation and RS20/75-63), Association pour la Recherche contre le Cancer (ARC PJA20191209650), EPIC-XS, project number 823839, funded by the Horizon 2020 programme of the European Union (PRC-5074) and FRM-Piraud prize to E.L., Bio-SPC “Contrat Doctoral” PhD fellowship to S.P., LNCC PhD fellowship to D.H., the Vancouver Prostate Centre to M.D., and Team Finn and The Ride to Concur Cancer to P.H.S., Fundings from ANR to A.A. ("ImmunoMeca" ANR-12-BSV5-0007-01, "Initiatives d’excellence" Idex ANR-11-IDEX-0005-02, and "Labex Who Am I?" ANR-11-LABX-0071)and to F.L. (ANR-10-EQPX-04-01), and from FEDER (12001407) to F.L. B.L. acknowledges financial supports from the Mechanobiology Institute, the European Research Council under the European Union's 7th Framework Programme (FP7/2007-2013) / ERC n° 617233 and NUS-USPC collaborative program.; ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011); ANR-12-BSV5-0007,ImmunoMeca,Caractérisation du rôle de la mécanique dans l'immunité: vers un modèle intégré de l'activation des cellules T(2012); ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011); ANR-11-LABX-0071,WHO AM I,Determinants de l'Identité : de la molécule à l'individu(2011); ANR-10-EQPX-0004,Imaginex BioMed,Plateau de microscopie de criblage à haut débit et d'analyse à très haute résolution(2010); European Project: 617233,ERC-2013-CoG,ERC-2013-CoG,DURACELL(2014) |
| Source: |
ISSN: 2041-1723. |
| Publisher Information: |
CCSD; Nature Publishing Group |
| Publication Year: |
2022 |
| Subject Terms: |
Rac1 GTPase; Mechanotransduction; Integrin signalling; CNF1 toxin; Hostpathogen interaction; Tumour suppressor; E3 ubiquitin ligase; [SDV]Life Sciences [q-bio]; [SDV.BC]Life Sciences [q-bio]/Cellular Biology; [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology |
| Description: |
International audience ; Extracellular matrix (ECM) elasticity is perceived by cells via focal adhesion structures, which transduce mechanical cues into chemical signalling to conform cell behaviour. Although the contribution of ECM compliance to the control of cell migration or division has been extensively studied, little has been reported regarding infectious processes. We have studied how mechanical properties of the ECM impact invasion of cells by the extraintestinal Escherichia coli pathogen UTI89. We show that UTI89 takes advantage, via its CNF1 toxin, of integrin mechanoactivation to trigger its invasion into cells. We identified OPTN as a protein regulated by ECM stiffness whose function is required for bacterial invasion and integrin mechanical coupling and for stimulation of HACE1 E3 ligase activity towards the Rac1 GTPase. We showed that OPTN knockdown cells display enhanced Rac1 activation, strong mechanochemical adhesion signalling and increased cyclin D1 translation, together with enhanced cell proliferation independent of ECM stiffness. Despite such features, OPTN knockdown cells displayed defective traction force buildup associated with limited cellular invasion by UTI89. Together, our data indicate that OPTN, through a new role in mechanobiology, supports CNF1-producing uropathogenic E. coli invasion and links HACE1-mediated ubiquitylation of Rac1 to ECM mechanical properties and integrin mechanotransduction. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/36229487; info:eu-repo/grantAgreement//617233/EU/Cell Migration under Mechanical Constraints/DURACELL; PUBMED: 36229487; PUBMEDCENTRAL: PMC9561704 |
| DOI: |
10.1038/s41467-022-33803-x |
| Availability: |
https://pasteur.hal.science/pasteur-03375882; https://pasteur.hal.science/pasteur-03375882v2/document; https://pasteur.hal.science/pasteur-03375882v2/file/s41467-022-33803-x.pdf; https://doi.org/10.1038/s41467-022-33803-x |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.86ACA45A |
| Database: |
BASE |