Axin1 Prevents Salmonella Invasiveness and Inflammatory Response in Intestinal Epithelial Cells

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Apr 18

PMID 22509369

Citations 18

Authors

Yong-Guo Zhang

Shaoping Wu

Yinglin Xia

Di Chen

Elaine O Petrof

Erika C Claud

Wei Hsu

Jun Sun

Affiliations

Soon will be listed here.

Abstract

Background: Axin1 and its homolog Axin2 are scaffold proteins essential for regulating Wnt signaling. Axin-dependent regulation of Wnt is important for various developmental processes and human diseases. However, the involvement of Axin1 and Axin2 in host defense and inflammation remains to be determined.

Methods/principal Findings: Here, we report that Axin1, but not Axin2, plays an essential role in host-pathogen interaction mediated by the Wnt pathway. Pathogenic Salmonella colonization greatly reduces the level of Axin1 in intestinal epithelial cells. This reduction is regulated at the posttranslational level in early onset of the bacterial infection. Further analysis reveals that the DIX domain and Ser614 of Axin1 are necessary for the Salmonella-mediated modulation through ubiquitination and SUMOylation.

Conclusion/significance: Axin1 apparently has a preventive effect on bacterial invasiveness and inflammatory response during the early stages of infection. The results suggest a distinct biological function of Axin1 and Axin2 in infectious disease and intestinal inflammation while they are functionally equivalent in developmental settings.

Citing Articles

Intestinal Epithelial Axin1 Deficiency Protects Against Colitis via Altered Gut Microbiota.

Garrett S, Zhang Y, Xia Y, Sun J Engineering (Beijing). 2024; 35:241-256.

PMID: 38911180 PMC: 11192507. DOI: 10.1016/j.eng.2023.06.007.

Axin1's mystique in manipulating microbiome amidst colitis.

Garrett S, Asada M, Sun J Gut Microbes. 2023; 15(2):2286674.

PMID: 38010886 PMC: 10730173. DOI: 10.1080/19490976.2023.2286674.

Roles of host SUMOylation in bacterial pathogenesis.

Ma X, Zhao C, Xu Y, Zhang H Infect Immun. 2023; 91(10):e0028323.

PMID: 37725062 PMC: 10580907. DOI: 10.1128/iai.00283-23.

Axin1: A novel scaffold protein joins the antiviral network of interferon.

Guo Y, Bamunuarachchi G, Vaddadi K, Zhu Z, Gandikota C, Ahmed K Mol Microbiol. 2022; 118(6):731-743.

PMID: 36308071 PMC: 9789182. DOI: 10.1111/mmi.14995.

The chromosome-scale genome of the raccoon dog: Insights into its evolutionary characteristics.

Lan T, Li H, Yang S, Shi M, Han L, Sahu S iScience. 2022; 25(10):105117.

PMID: 36185367 PMC: 9523411. DOI: 10.1016/j.isci.2022.105117.

References

Yu H, Jerchow B, Sheu T, Liu B, Costantini F, Puzas J . The role of Axin2 in calvarial morphogenesis and craniosynostosis. Development. 2005; 132(8):1995-2005. PMC: 1828115. DOI: 10.1242/dev.01786. View

Nakamura T, Hamada F, ISHIDATE T, Anai K, Kawahara K, Toyoshima K . Axin, an inhibitor of the Wnt signalling pathway, interacts with beta-catenin, GSK-3beta and APC and reduces the beta-catenin level. Genes Cells. 1998; 3(6):395-403. DOI: 10.1046/j.1365-2443.1998.00198.x. View

Liu X, Wu S, Xia Y, Li X, Xia Y, Zhou Z . Wingless homolog Wnt11 suppresses bacterial invasion and inflammation in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2011; 301(6):G992-G1003. PMC: 3233790. DOI: 10.1152/ajpgi.00080.2011. View

Wehkamp J, Wang G, Kubler I, Nuding S, Gregorieff A, Schnabel A . The Paneth cell alpha-defensin deficiency of ileal Crohn's disease is linked to Wnt/Tcf-4. J Immunol. 2007; 179(5):3109-18. DOI: 10.4049/jimmunol.179.5.3109. View

Luo W, Zou H, Jin L, Lin S, Li Q, Ye Z . Axin contains three separable domains that confer intramolecular, homodimeric, and heterodimeric interactions involved in distinct functions. J Biol Chem. 2004; 280(6):5054-60. DOI: 10.1074/jbc.M412340200. View

Mao J, Wang J, Liu B, Pan W, Farr 3rd G, Flynn C . Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway. Mol Cell. 2001; 7(4):801-9. DOI: 10.1016/s1097-2765(01)00224-6. View

Logan C, Nusse R . The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004; 20:781-810. DOI: 10.1146/annurev.cellbio.20.010403.113126. View

Zhang Y, Neo S, Han J, Lin S . Dimerization choices control the ability of axin and dishevelled to activate c-Jun N-terminal kinase/stress-activated protein kinase. J Biol Chem. 2000; 275(32):25008-14. DOI: 10.1074/jbc.M002491200. View

Wu S, Liao A, Xia Y, Li Y, Li J, Sartor R . Vitamin D receptor negatively regulates bacterial-stimulated NF-kappaB activity in intestine. Am J Pathol. 2010; 177(2):686-97. PMC: 2913341. DOI: 10.2353/ajpath.2010.090998. View

10.

Sun J, Hobert M, Rao A, Neish A, Madara J . Bacterial activation of beta-catenin signaling in human epithelia. Am J Physiol Gastrointest Liver Physiol. 2004; 287(1):G220-7. DOI: 10.1152/ajpgi.00498.2003. View

11.

Hsu W, Zeng L, Costantini F . Identification of a domain of Axin that binds to the serine/threonine protein phosphatase 2A and a self-binding domain. J Biol Chem. 1999; 274(6):3439-45. DOI: 10.1074/jbc.274.6.3439. View

12.

Yamamoto H, Kishida S, Uochi T, Ikeda S, Koyama S, Asashima M . Axil, a member of the Axin family, interacts with both glycogen synthase kinase 3beta and beta-catenin and inhibits axis formation of Xenopus embryos. Mol Cell Biol. 1998; 18(5):2867-75. PMC: 110665. DOI: 10.1128/MCB.18.5.2867. View

13.

Clevers H . Wnt/beta-catenin signaling in development and disease. Cell. 2006; 127(3):469-80. DOI: 10.1016/j.cell.2006.10.018. View

14.

Yu H, Liu B, Costantini F, Hsu W . Impaired neural development caused by inducible expression of Axin in transgenic mice. Mech Dev. 2006; 124(2):146-56. PMC: 1847614. DOI: 10.1016/j.mod.2006.10.002. View

15.

Liu X, Lu R, Wu S, Zhang Y, Xia Y, Sartor R . Wnt2 inhibits enteric bacterial-induced inflammation in intestinal epithelial cells. Inflamm Bowel Dis. 2011; 18(3):418-29. PMC: 3294455. DOI: 10.1002/ibd.21788. View

16.

Kishida S, Yamamoto H, Ikeda S, Kishida M, Sakamoto I, Koyama S . Axin, a negative regulator of the wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates the stabilization of beta-catenin. J Biol Chem. 1998; 273(18):10823-6. DOI: 10.1074/jbc.273.18.10823. View

17.

MILLER S, Mekalanos J . Constitutive expression of the phoP regulon attenuates Salmonella virulence and survival within macrophages. J Bacteriol. 1990; 172(5):2485-90. PMC: 208887. DOI: 10.1128/jb.172.5.2485-2490.1990. View

18.

Schaale K, Neumann J, Schneider D, Ehlers S, Reiling N . Wnt signaling in macrophages: augmenting and inhibiting mycobacteria-induced inflammatory responses. Eur J Cell Biol. 2010; 90(6-7):553-9. DOI: 10.1016/j.ejcb.2010.11.004. View

19.

Behrens J, Jerchow B, Wurtele M, Grimm J, Asbrand C, Wirtz R . Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta. Science. 1998; 280(5363):596-9. DOI: 10.1126/science.280.5363.596. View

20.

Liao A, Petrof E, Kuppireddi S, Zhao Y, Xia Y, Claud E . Salmonella type III effector AvrA stabilizes cell tight junctions to inhibit inflammation in intestinal epithelial cells. PLoS One. 2008; 3(6):e2369. PMC: 2408728. DOI: 10.1371/journal.pone.0002369. View