ArticlePLoS pathogens2013
Pasteurella multocida toxin prevents osteoblast differentiation by transactivation of the MAP-kinase cascade via the Gα(q/11)--p63RhoGEF--RhoA axis.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- CXCL8 Knockout: A Key to ResistingInternational journal of molecular sciences · 2024Article
- Revealing the lethal effects ofFrontiers in microbiology · 2024Article
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- Pasteurella multocida toxin - lessons learned from a mitogenic toxin.Frontiers in immunology · 2022Review
- In Vivo Targets ofInternational journal of molecular sciences · 2020Article
- The bacterial Ras/Rap1 site-specific endopeptidase RRSP cleaves Ras through an atypical mechanism to disrupt Ras-ERK signaling.Science signaling · 2018Article
- Involvement of Osteocytes in the Action ofToxins · 2018Article
- Salmonella Typhimurium effector SseI inhibits chemotaxis and increases host cell survival by deamidation of heterotrimeric Gi proteins.PLoS pathogens · 2018Article
- YopT domain of the PfhB2 toxin from Pasteurella multocida: protein expression, characterization, crystallization and crystallographic analysis.Acta crystallographica. Section F, Structural biology communications · 2018Article
- Hot-spot identification on a broad class of proteins and RNA suggest unifying principles of molecular recognition.PloS one · 2017Article
- Article
- Selective Membrane Redistribution and Depletion of Gαq-Protein by Pasteurella multocida Toxin.Toxins · 2016Article
- Ciliary IFT80 balances canonical versus non-canonical hedgehog signalling for osteoblast differentiation.Nature communications · 2016Article
- Article
- Strike a pose: Gαq complexes at the membrane.Trends in pharmacological sciences · 2014Review
- Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The 146-kDa Pasteurella multocida toxin (PMT) is the main virulence factor to induce P. multocida-associated progressive atrophic rhinitis in various animals. PMT leads to a destruction of nasal turbinate bones implicating an effect of the toxin on osteoblasts and/or osteoclasts. The toxin induces constitutive activation of Gα proteins of the G(q/11)-, G₁₂/₁₃- and G(i)-family by deamidating an essential glutamine residue. To study the PMT effect on bone cells, we used primary osteoblasts derived from rat calvariae and stromal ST-2 cells as differentiation model. As marker of functional osteoblasts the expression and activity of alkaline phosphatase, formation of mineralization nodules or expression of specific transcription factors as osterix was determined. Here, we show that the toxin inhibits differentiation and/or function of osteoblasts by activation of Gα(q/11). Subsequently, Gα(q/11) activates RhoA via p63RhoGEF, which specifically interacts with Gα(q/11) but not with other G proteins like Gα₁₂/₁₃ and Gα(i). Activated RhoA transactivates the mitogen-activated protein (MAP) kinase cascade via Rho kinase, involving Ras, MEK and ERK, resulting in inhibition of osteoblast differentiation. PMT-induced inhibition of differentiation was selective for the osteoblast lineage as adipocyte-like differentiation of ST-2 cells was not hampered. The present work provides novel insights, how the bacterial toxin PMT can control osteoblastic development by activating heterotrimeric G proteins of the Gα(q/11)-family and is a molecular pathogenetic basis for understanding the role of the toxin in bone loss during progressive atrophic rhinitis induced by Pasteurella multocida.
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