Nature communications, 2022-10, Vol.13 (1), p.6059-6059, Article 6059
2022
Details
- Autor(en) / Beteiligte
- Titel
- Optineurin links Hace1-dependent Rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division
- Ist Teil von
- Nature communications, 2022-10, Vol.13 (1), p.6059-6059, Article 6059
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2022
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Extracellular matrix (ECM) elasticity is perceived by cells via focal adhesion structures, which transduce mechanical cues into chemical signalling to conform cell behavior. Although the contribution of ECM compliance to the control of cell migration or division is extensively studied, little is reported regarding infectious processes. We study this phenomenon with 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 identify the HACE1 E3 ligase-interacting protein Optineurin (OPTN) as a protein regulated by ECM stiffness. Functional analysis establishes a role of OPTN in bacterial invasion and integrin mechanical coupling and for stimulation of HACE1 E3 ligase activity towards the Rac1 GTPase. Consistent with a role of OPTN in cell mechanics, OPTN knockdown cells display defective integrin-mediated traction force buildup, associated with limited cellular invasion by UTI89. Nevertheless, OPTN knockdown cells display strong mechanochemical adhesion signalling, enhanced Rac1 activation and increased cyclin D1 translation, together with enhanced cell proliferation independent of ECM stiffness. Together, our data ascribe a new function to OPTN in mechanobiology.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-022-33803-xTitel-ID: cdi_doaj_primary_oai_doaj_org_article_1958110237ff42f391f49c167f39e785
- Format
- –
- Schlagworte
- Actin, Adhesion, Adhesive strength, Bacteria, Bacteriology, Cell Division, Cell migration, Cell proliferation, Cellular Biology, Cyclin D1, Cyclin D1 - metabolism, Cytoskeleton, E coli, Escherichia coli, Extracellular matrix, Functional analysis, Integrins - metabolism, Life Sciences, Mechanical properties, Mechanotransduction, Mechanotransduction, Cellular - physiology, Microbiology and Parasitology, Modulus of elasticity, Proteins, rac1 GTP-Binding Protein - metabolism, Rac1 protein, Signaling, Stiffness, Toxins, Traction force, Ubiquitin, Ubiquitin-protein ligase, Ubiquitin-Protein Ligases - metabolism, Ubiquitination, Urinary tract