Dataset Information

The role of anthrax toxin protein receptor 1 as a new mechanosensor molecule and its mechanotransduction in BMSCs under hydrostatic pressure.

ABSTRACT: Anthrax toxin protein receptor (ANTXR) 1 has many similarities to integrin and is regarded in some respects as a single-stranded integrin protein. However, it is not clear whether ANTXR1 responds to mechanical signals secondary to the activation of integrins or whether it is a completely new, independent and previously undiscovered mechanosensor that responds to an undefined subset of mechanical signaling molecules. Our study demonstrates that ANTXR1 is a novel mechanosensor on the cell membrane, acting independently from the classical mechanoreceptor molecule integrin?1. We show that bone marrow stromal cells (BMSCs) respond to the hydrostatic pressure towards chondrogenic differentiation partly through the glycogen synthase kinase (GSK) 3?/?-Catenin signaling pathway, which can be partly regulated by ANTXR1 and might be related to the direct binding between ANTXR1 and low-density lipoprotein receptor-related protein (LRP) 5/6. In addition, ANTXR1 specifically activates Smad2 and upregulates Smad4 expression to facilitate the transport of activated Smad2 to the nucleus to regulate chondrogenesis, which might be related to the direct binding between ANTXR1 and Actin/Fascin1. We also demonstrate that ANTXR1 binds to some extent with integrin?1, but this interaction does not affect the expression and function of either protein under pressure. Thus, we conclude that ANTXR1 plays a crucial role in BMSC mechanotransduction and controls specific signaling pathways that are distinct from those of integrin to influence the chondrogenic responses of BMSCs under hydrostatic pressure.

SUBMITTER: Cheng B

PROVIDER: S-EPMC6718418 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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The role of anthrax toxin protein receptor 1 as a new mechanosensor molecule and its mechanotransduction in BMSCs under hydrostatic pressure.

Cheng Baixiang B Liu Yanzheng Y Zhao Ying Y Li Qiang Q Liu Yanli Y Wang Junjun J Chen Yongjin Y Zhang Min M

Scientific reports 20190902 1

Anthrax toxin protein receptor (ANTXR) 1 has many similarities to integrin and is regarded in some respects as a single-stranded integrin protein. However, it is not clear whether ANTXR1 responds to mechanical signals secondary to the activation of integrins or whether it is a completely new, independent and previously undiscovered mechanosensor that responds to an undefined subset of mechanical signaling molecules. Our study demonstrates that ANTXR1 is a novel mechanosensor on the cell membrane ...[more]

PMID: 31477767

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Project description:The discovery of hyperthermophiles has dramatically changed our understanding of the habitats in which life can thrive. However, the extreme high temperatures in which these organisms live have severely restricted the development of genetic tools. The archaeon Pyrococcus yayanosii A1 is a strictly anaerobic and piezophilic hyperthermophile that is an ideal model for studies of extreme environmental adaptation. In the present study, we identified a high hydrostatic pressure (HHP)-inducible promoter (P hhp ) that controls target gene expression under HHP. We developed an HHP-inducible toxin-antitoxin cassette (HHP-TAC) containing (i) a counterselectable marker in which a gene encoding a putative toxin (virulence-associated protein C [PF0776 {VapC}]) controlled by the HHP-inducible promoter was used in conjunction with the gene encoding antitoxin PF0775 (VapB), which was fused to a constitutive promoter (P hmtB ), and (ii) a positive marker with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase-encoding gene from P. furiosus controlled by the constitutive promoter P gdh The HHP-TAC was constructed to realize markerless gene disruption directly in P. yayanosii A1 in rich medium. The pop-out recombination step was performed using an HHP-inducible method. As proof, the PYCH_13690 gene, which encodes a 4-α-glucanotransferase, was successfully deleted from the strain P. yayanosii A1. The results showed that the capacity for starch hydrolysis in the Δ1369 mutant decreased dramatically compared to that in the wild-type strain. The inducible toxin-antitoxin system developed in this study greatly increases the genetic tools available for use in hyperthermophiles.IMPORTANCE Genetic manipulations in hyperthermophiles have been studied for over 20 years. However, the extremely high temperatures under which these organisms grow have limited the development of genetic tools. In this study, an HHP-inducible promoter was used to control the expression of a toxin. Compared to sugar-inducible and cold-shock-inducible promoters, the HHP-inducible promoter rarely has negative effects on the overall physiology and central metabolism of microorganisms, especially piezophilic hyperthermophiles. Previous studies have used auxotrophic strains as hosts, which may interfere with studies of adaptation and metabolism. Using an inducible toxin-antitoxin (TA) system as a counterselectable marker enables the generation of a markerless gene disruption strain without the use of auxotrophic mutants and counterselection with 5-fluoroorotic acid. TA systems are widely distributed in bacteria and archaea and can be used to overcome the limitations of high growth temperatures and dramatically extend the selectivity of genetic tools in hyperthermophiles.

Dataset Information

The role of anthrax toxin protein receptor 1 as a new mechanosensor molecule and its mechanotransduction in BMSCs under hydrostatic pressure.

Publications

The role of anthrax toxin protein receptor 1 as a new mechanosensor molecule and its mechanotransduction in BMSCs under hydrostatic pressure.

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