Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Integrin Alpha11 (ITGA11)

  • Cédric ZeltzEmail author
  • Donald Gullberg
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_118


Historical Background

Integrin α11 is the last member of the integrin family to be discovered. This integrin subunit was initially named αmt, since it was first identified in human fetal myotube cultures (Gullberg et al. 1995). In 1999, the β1-associated α11integrin was characterized as a collagen-binding integrin and human α11 cDNA was sequenced (Velling et al. 1999). Two years later, Tiger et al. described the α11β1 integrin as a collagen receptor involved in cell migration and collagen reorganization (Tiger et al. 2001). The generation of α11−/− integrin mice was a major advance in the efforts to elucidate α11 integrin function in health and disease (Popova et al. 2007a, b; Zeltz and Gullberg 2016).

Gene and Protein Structure of the α11 Integrin

The human α11 integrin gene (ITGA11) is localized on chromosome 15q23 and consists of 130 kb, whereas the mouse α11 integrin gene (Itga11; length of 106 kb) has been...

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  1. Barczyk MM, Olsen LH, da Franca P, Loos BG, Mustafa K, Gullberg D, et al. A role for alpha11beta1 integrin in the human periodontal ligament. J Dent Res. 2009;88(7):621–6.CrossRefPubMedGoogle Scholar
  2. Barczyk M, Bolstad AI, Gullberg D. Role of integrins in the periodontal ligament: organizers and facilitators. Periodontol 2000. 2013a;63(1):29–47.Google Scholar
  3. Barczyk MM, Lu N, Popova SN, Bolstad AI, Gullberg D. alpha11beta1 integrin-mediated MMP-13-dependent collagen lattice contraction by fibroblasts: evidence for integrin-coordinated collagen proteolysis. J Cell Physiol. 2013b;228:1108–19.CrossRefPubMedGoogle Scholar
  4. Bengtsson T, Camper L, Schneller M, Lundgren-Akerlund E. Characterization of the mouse integrin subunit a10 gene and comparison with its human homologue. Genomic structure, chromosomal localization and identification of splice variants. Matrix Biol. 2001;20(8):565–76.CrossRefPubMedGoogle Scholar
  5. Blumbach K, Niehoff A, Belgardt BF, Ehlen HW, Schmitz M, Hallinger R, et al. Dwarfism in mice lacking collagen-binding integrins alpha2beta1 and alpha11beta1 is caused by severely diminished IGF-1 levels. J Biol Chem. 2012;287(9):6431–40.CrossRefPubMedGoogle Scholar
  6. Bray PF. Platelet glycoprotein polymorphisms as risk factors for thrombosis. Curr Opin Hematol. 2000;7(5):284–9.CrossRefPubMedGoogle Scholar
  7. Carracedo S, Lu N, Popova SN, Jonsson R, Eckes B, Gullberg D. The fibroblast integrin alpha11beta1 is induced in a mechanosensitive manner involving activin A and regulates myofibroblast differentiation. J Biol Chem. 2010;285(14):10434–45.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Caswell CC, Barczyk M, Keene DR, Lukomska E, Gullberg DE, Lukomski S. Identification of the first prokaryotic collagen sequence motif that mediates binding to human collagen receptors, integrins alpha2beta1 and alpha11beta1. J Biol Chem. 2008;283(52):36168–75.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Civitarese RA, Talior-Volodarsky I, Desjardins JF, Kabir G, Switzer J, Mitchell M, et al. The alpha11 integrin mediates fibroblast-extracellular matrix-cardiomyocyte interactions in health and disease. Am J Physiol Heart Circ Physiol. 2016;311(1):H96–H106.CrossRefPubMedGoogle Scholar
  10. Grella A, Kole D, Holmes W, Dominko T. FGF2 overrides TGFbeta1-driven integrin ITGA11 expression in human dermal fibroblasts. J Cell Biochem. 2016;117(4):1000–8.CrossRefPubMedGoogle Scholar
  11. Gullberg D, Velling T, Sjoberg G, Sejersen T. Up-regulation of a novel integrin alpha-chain (alpha mt) on human fetal myotubes. Dev Dyn. 1995;204(1):57–65.CrossRefPubMedGoogle Scholar
  12. Kaltz N, Ringe J, Holzwarth C, Charbord P, Niemeyer M, Jacobs VR, et al. Novel markers of mesenchymal stem cells defined by genome-wide gene expression analysis of stromal cells from different sources. Exp Cell Res. 2010;316(16):2609–17.CrossRefPubMedGoogle Scholar
  13. Leomil Coelho LF, Mota BE, Sales PC, Marques JT, de Oliveira JG, Bonjardim CA, et al. Integrin alpha 11 is a novel type I interferon stimulated gene. Cytokine. 2006;33(6):352–61.CrossRefPubMedGoogle Scholar
  14. Lu N, Heuchel R, Barczyk M, Zhang WM, Gullberg D. Tandem Sp1/Sp3 sites together with an Ets-1 site cooperate to mediate alpha11 integrin chain expression in mesenchymal cells. Matrix Biol. 2006;25(2):118–29.CrossRefPubMedGoogle Scholar
  15. Lu N, Carracedo S, Ranta J, Heuchel R, Soininen R, Gullberg D. The human alpha11 integrin promoter drives fibroblast-restricted expression in vivo and is regulated by TGF-beta1 in a Smad- and Sp1-dependent manner. Matrix Biol. 2010;29(3):166–76.CrossRefPubMedGoogle Scholar
  16. Lu N, Karlsen TV, Reed RK, Kusche-Gullberg M, Gullberg D. Fibroblast alpha11beta1 integrin regulates tensional homeostasis in fibroblast/A549 carcinoma heterospheroids. PLoS One. 2014;9(7):e103173.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Navab R, Strumpf D, To C, Pasko E, Kim KS, Park CJ, et al. Integrin alpha11beta1 regulates cancer stromal stiffness and promotes tumorigenicity and metastasis in non-small cell lung cancer. Oncogene. 2015.  https://doi.org/10.1038/onc.2015.254.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Parmar PG, Taal HR, Timpson NJ, Thiering E, Lehtimaki T, Marinelli M, et al. International Genome-Wide Association Study Consortium identifies novel loci associated with blood pressure in children and adolescents. Circ Cardiovasc Genet. 2016;9(3):266–78.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Pellinen T, Arjonen A, Vuoriluoto K, Kallio K, Fransen JA, Ivaska J. Small GTPase Rab21 regulates cell adhesion and controls endosomal traffic of beta1-integrins. J Cell Biol. 2006;173(5):767–80.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Popov C, Radic T, Haasters F, Prall WC, Aszodi A, Gullberg D, et al. Integrins alpha2beta1 and alpha11beta1 regulate the survival of mesenchymal stem cells on collagen I. Cell Death Dis. 2011;2:e186.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Popova SN, Rodriguez-Sanchez B, Liden A, Betsholtz C, Van Den Bos T, Gullberg D. The mesenchymal alpha11beta1 integrin attenuates PDGF-BB-stimulated chemotaxis of embryonic fibroblasts on collagens. Dev Biol. 2004;270(2):427–42.CrossRefPubMedGoogle Scholar
  22. Popova SN, Barczyk M, Tiger CF, Beertsen W, Zigrino P, Aszodi A, et al. Alpha11 beta1 integrin-dependent regulation of periodontal ligament function in the erupting mouse incisor. Mol Cell Biol. 2007a;27(12):4306–16.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Popova SN, Lundgren-Akerlund E, Wiig H, Gullberg D. Physiology and pathology of collagen receptors. Acta Physiol (Oxford). 2007b;190(3):179–87.CrossRefGoogle Scholar
  24. Porto Neto LR, Bunch RJ, Harrison BE, Prayaga KC, Barendse W. Haplotypes that include the integrin alpha 11 gene are associated with tick burden in cattle. BMC Genet. 2010;11:55.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Schulz JN, Zeltz C, Sorensen IW, Barczyk M, Carracedo S, Hallinger R, et al. Reduced granulation tissue and wound strength in the absence of alpha11beta1 integrin. J Invest Dermatol. 2015;135(5):1435–44.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Siljander PR, Hamaia S, Peachey AR, Slatter DA, Smethurst PA, Ouwehand WH, et al. Integrin activation state determines selectivity for novel recognition sites in fibrillar collagens. J BiolChem. 2004;279(46):47763–72.Google Scholar
  27. Talior-Volodarsky I, Connelly KA, Arora PD, Gullberg D, McCulloch CA. alpha11 integrin stimulates myofibroblast differentiation in diabetic cardiomyopathy. Cardiovasc Res. 2012;96(2):265–75.CrossRefPubMedGoogle Scholar
  28. Talior-Volodarsky I, Arora PD, Wang Y, Zeltz C, Connelly KA, Gullberg D, et al. Glycated collagen induces alpha11 integrin expression through TGF-beta2 and Smad3. J Cell Physiol. 2015;230:327–36.CrossRefPubMedGoogle Scholar
  29. Tiger CF, Fougerousse F, Grundstrom G, Velling T, Gullberg D. Alpha11beta1 integrin is a receptor for interstitial collagens involved in cell migration and collagen reorganization on mesenchymal nonmuscle cells. Dev Biol. 2001;237(1):116–29.CrossRefPubMedGoogle Scholar
  30. Varas L, Ohlsson LB, Honeth G, Olsson A, Bengtsson T, Wiberg C, et al. Alpha10 integrin expression is up-regulated on fibroblast growth factor-2-treated mesenchymal stem cells with improved chondrogenic differentiation potential. Stem Cells Dev. 2007;16(6):965–78.CrossRefPubMedGoogle Scholar
  31. Velling T, Kusche-Gullberg M, Sejersen T, Gullberg D. cDNA cloning and chromosomal localization of human alpha11 integrin. A collagen-binding, I domain-containing, beta1-associated integrin alpha-chain present in muscle tissues. J Biol Chem. 1999;274(36):25735–42.CrossRefPubMedGoogle Scholar
  32. Wang KK, Liu N, Radulovich N, Wigle DA, Johnston MR, Shepherd FA, et al. Novel candidate tumor marker genes for lung adenocarcinoma. Oncogene. 2002;21(49):7598–604.CrossRefPubMedGoogle Scholar
  33. Westcott JM, Prechtl AM, Maine EA, Dang TT, Esparza MA, Sun H, et al. An epigenetically distinct breast cancer cell subpopulation promotes collective invasion. J Clin Invest. 2015;125(5):1927–43.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Xie C, Shimaoka M, Xiao T, Schwab P, Klickstein LB, Springer TA. The integrin alpha-subunit leg extends at a Ca2+−dependent epitope in the thigh/genu interface upon activation. Proc Natl Acad Sci USA. 2004;101(43):15422–7.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Zeltz C, Gullberg D. The integrin-collagen connection - a glue for tissue repair? J Cell Sci. 2016;129(4):653–64.CrossRefPubMedGoogle Scholar
  36. Zhang WM, Kapyla J, Puranen JS, Knight CG, Tiger CF, Pentikainen OT, et al. Alpha11beta1 integrin recognizes the GFOGER sequence in interstitial collagens. J Biol Chem. 2003;278(9):7270–7.CrossRefPubMedGoogle Scholar
  37. Zhang ZG, Bothe I, Hirche F, Zweers M, Gullberg D, Pfitzer G, et al. Interactions of primary fibroblasts and keratinocytes with extracellular matrix proteins: contribution of alpha2beta1 integrin. J Cell Sci. 2006;119(Pt 9):1886–95.CrossRefPubMedGoogle Scholar
  38. Zhu CQ, Popova SN, Brown ER, Barsyte-Lovejoy D, Navab R, Shih W, et al. Integrin alpha 11 regulates IGF2 expression in fibroblasts to enhance tumorigenicity of human non-small-cell lung cancer cells. Proc Natl Acad Sci USA. 2007;104(28):11754–9.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Zweers MC, Davidson JM, Pozzi A, Hallinger R, Janz K, Quondamatteo F, et al. Integrin alpha2beta1 is required for regulation of murine wound angiogenesis but is dispensable for reepithelialization. J Invest Dermatol. 2007;127(2):467–78.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Princess Margaret Cancer CenterUniversity Health NetworkToronto, ONCanada
  2. 2.Department of BiomedicineUniversity of BergenBergenNorway