Fibronectin receptor functions in embryonic cells deficient in alpha 5 beta 1 integrin can be replaced by alpha V integrins

JT Yang and RO Hynes

Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts, USA.

alpha 5 beta 1 integrin mediates cell adhesion to extracellular matrix by interacting with fibronectin (FN). Mouse lines carrying null mutations in genes encoding either the alpha 5 integrin subunit or FN have been generated previously. Both mutations are embryonic lethal with overlapping defects, but the defects of alpha 5-null embryos are less severe. Primary embryonic cells lacking alpha 5 beta 1 are able to adhere to FN, form focal contacts, migrate on FN, and assemble FN matrix. These results suggest the involvement of (an)other FN receptors(s). In this study, we examined functions of alpha 4 beta 1 and alpha V integrins in embryonic cells lacking alpha 5 beta 1. Our analysis of cells lacking both alpha 4 beta 1 and alpha 5 beta 1 showed that alpha 4 beta 1 is also not required for these FN-dependent functions. Using alpha V-specific blocking reagents, we showed that alpha V integrins are required for alpha 5-null cells, but not wild- type cells, to adhere and spread on FN. Our data also showed that, although the expression levels of alpha V integrins on the wild-type and alpha 5-null cells are similar, there is an increase in recruitment of alpha V integrins into focal contacts in alpha 5-null cells plated on FN, indicating that alpha V integrins can compensate functionally for the loss of alpha 5 beta 1 in focal contacts of alpha 5-null cells. Finally, our data suggested possible roles for alpha V integrins in replacing the role of alpha 5 beta 1 in FN matrix assembly in vitro and in FN-dependent embryonic functions in vivo.

Volume 7, Issue 11, pp. 1737-1748, 11/01/1996
Copyright © 1996 by The American Society for Cell Biology

This article has been cited by other articles:

				S. Huveneers, H. Truong, R. Fassler, A. Sonnenberg, and E. H. J. Danen Binding of soluble fibronectin to integrin {alpha}5{beta}1 - link to focal adhesion redistribution and contractile shape J. Cell Sci., August 1, 2008; 121(15): 2452 - 2462. [Abstract] [Full Text] [PDF]

				T. R. Carlson, H. Hu, R. Braren, Y. H. Kim, and R. A. Wang Cell-autonomous requirement for {beta}1 integrin in endothelial cell adhesion, migration and survival during angiogenesis in mice Development, June 15, 2008; 135(12): 2193 - 2202. [Abstract] [Full Text] [PDF]

				G. H. Mahabeleshwar, W. Feng, D. R. Phillips, and T. V. Byzova Integrin signaling is critical for pathological angiogenesis J. Exp. Med., October 30, 2006; 203(11): 2495 - 2507. [Abstract] [Full Text] [PDF]

				N. E. Winterwood, A. Varzavand, M. N. Meland, L. K. Ashman, and C. S. Stipp A Critical Role for Tetraspanin CD151 in {alpha}3beta1 and {alpha}6beta4 Integrin-dependent Tumor Cell Functions on Laminin-5 Mol. Biol. Cell, June 1, 2006; 17(6): 2707 - 2721. [Abstract] [Full Text] [PDF]

				E. H.J. Heerkens, L. Shaw, A. Ryding, G. Brooker, J. J. Mullins, C. Austin, V. Ohanian, and A. M. Heagerty {alpha}V Integrins Are Necessary for Eutrophic Inward Remodeling of Small Arteries in Hypertension Hypertension, February 1, 2006; 47(2): 281 - 287. [Abstract] [Full Text] [PDF]

				Y. Mao and J. E. Schwarzbauer Stimulatory effects of a three-dimensional microenvironment on cell-mediated fibronectin fibrillogenesis J. Cell Sci., October 1, 2005; 118(19): 4427 - 4436. [Abstract] [Full Text] [PDF]

				Z. Li, X. Chen, Y. Xie, S. Shi, Z. Feng, B. Fu, X. Zhang, G. Cai, C. Wu, D. Wu, et al. Expression and Significance of Integrin-Linked Kinase in Cultured Cells, Normal Tissue, and Diseased Tissue of Aging Rat Kidneys J. Gerontol. A Biol. Sci. Med. Sci., October 1, 2004; 59(10): B984 - B996. [Abstract] [Full Text] [PDF]

				E. E. Robinson, R. A. Foty, and S. A. Corbett Fibronectin Matrix Assembly Regulates {alpha}5{beta}1-mediated Cell Cohesion Mol. Biol. Cell, March 1, 2004; 15(3): 973 - 981. [Abstract] [Full Text] [PDF]

				E. H.J. Danen, P. Sonneveld, C. Brakebusch, R. Fassler, and A. Sonnenberg The fibronectin-binding integrins {alpha}5{beta}1 and {alpha}v{beta}3 differentially modulate RhoA-GTP loading, organization of cell matrix adhesions, and fibronectin fibrillogenesis J. Cell Biol., December 23, 2002; 159(6): 1071 - 1086. [Abstract] [Full Text] [PDF]

				K. A. Pinco, W. He, and J. T. Yang alpha 4beta 1 Integrin Regulates Lamellipodia Protrusion via a Focal Complex/Focal Adhesion-independent Mechanism Mol. Biol. Cell, September 1, 2002; 13(9): 3203 - 3217. [Abstract] [Full Text] [PDF]

				S. S. Akimov and A. M. Belkin Cell-surface transglutaminase promotes fibronectin assembly via interaction with the gelatin-binding domain of fibronectin: a role in TGF{beta}-dependent matrix deposition J. Cell Sci., March 10, 2002; 114(16): 2989 - 3000. [Abstract] [Full Text] [PDF]

				D. R. Senger, C. A. Perruzzi, M. Streit, V. E. Koteliansky, A. R. de Fougerolles, and M. Detmar The {alpha}1{beta}1 and {alpha}2{beta}1 Integrins Provide Critical Support for Vascular Endothelial Growth Factor Signaling, Endothelial Cell Migration, and Tumor Angiogenesis Am. J. Pathol., January 1, 2002; 160(1): 195 - 204. [Abstract] [Full Text] [PDF]

				L. Guo, P. W. Sanders, A. Woods, and C. Wu The Distribution and Regulation of Integrin-Linked Kinase in Normal and Diabetic Kidneys Am. J. Pathol., November 1, 2001; 159(5): 1735 - 1742. [Abstract] [Full Text] [PDF]

				S. F. Retta, G. Cassara, M. D'Amato, R. Alessandro, M. Pellegrino, S. Degani, G. De Leo, L. Silengo, and G. Tarone Cross Talk between beta 1 and alpha V Integrins: beta 1 Affects beta 3 mRNA Stability Mol. Biol. Cell, October 1, 2001; 12(10): 3126 - 3138. [Abstract] [Full Text] [PDF]

				P. A. Rupp and C. D. Little Integrins in Vascular Development Circ. Res., September 28, 2001; 89(7): 566 - 572. [Abstract] [Full Text] [PDF]

				O. E. Olorundare, O. Peyruchaud, R. M. Albrecht, and D. F. Mosher Assembly of a fibronectin matrix by adherent platelets stimulated by lysophosphatidic acid and other agonists Blood, July 1, 2001; 98(1): 117 - 124. [Abstract] [Full Text] [PDF]

				A. G. Arroyo, D. Taverna, C. A. Whittaker, U. G. Strauch, B. L. Bader, H. Rayburn, D. Crowley, C. M. Parker, and R. O. Hynes In Vivo Roles of Integrins During Leukocyte Development and Traffic: Insights from the Analysis of Mice Chimeric for {alpha}5, {alpha}v, and {alpha}4 Integrins J. Immunol., October 15, 2000; 165(8): 4667 - 4675. [Abstract] [Full Text] [PDF]

				A. J. Coito, K. Onodera, H. Kato, R. W. Busuttil, and J. W. Kupiec-Weglinski Fibronectin-Mononuclear Cell Interactions Regulate Type 1 Helper T Cell Cytokine Network in Tolerant Transplant Recipients Am. J. Pathol., October 1, 2000; 157(4): 1207 - 1218. [Abstract] [Full Text] [PDF]

				J. A. Bowen and J. S. Hunt The Role of Integrins in Reproduction Experimental Biology and Medicine, April 1, 2000; 223(4): 331 - 343. [Abstract] [Full Text] [PDF]

				D. C. Hocking, J. Sottile, and K. J. Langenbach Stimulation of Integrin-mediated Cell Contractility by Fibronectin Polymerization J. Biol. Chem., March 31, 2000; 275(14): 10673 - 10682. [Abstract] [Full Text] [PDF]

				S. A. Corbett and J. E. Schwarzbauer Requirements for alpha 5beta 1 Integrin-mediated Retraction of Fibronectin-Fibrin Matrices J. Biol. Chem., July 23, 1999; 274(30): 20943 - 20948. [Abstract] [Full Text] [PDF]

				S Testaz, M Delannet, and J Duband Adhesion and migration of avian neural crest cells on fibronectin require the cooperating activities of multiple integrins of the (beta)1 and (beta)3 families J. Cell Sci., January 12, 1999; 112(24): 4715 - 4728. [Abstract] [PDF]

				Q. Zhang, T. Sakai, J. Nowlen, I. Hayashi, R. Fassler, and D. F. Mosher Functional beta 1-Integrins Release the Suppression of Fibronectin Matrix Assembly by Vitronectin J. Biol. Chem., January 1, 1999; 274(1): 368 - 375. [Abstract] [Full Text] [PDF]

				D. Taverna, M.-H. Disatnik, H. Rayburn, R. T. Bronson, J. Yang, T. A. Rando, and R. O. Hynes Dystrophic Muscle in Mice Chimeric for Expression of alpha 5 Integrin J. Cell Biol., November 2, 1998; 143(3): 849 - 859. [Abstract] [Full Text] [PDF]

				J. L. Sechler, S. A. Corbett, and J. E. Schwarzbauer Modulatory Roles for Integrin Activation and the Synergy Site of Fibronectin during Matrix Assembly Mol. Biol. Cell, December 1, 1997; 8(12): 2563 - 2573. [Abstract] [Full Text]

				C Brakebusch, E Hirsch, A Potocnik, and R Fassler Genetic analysis of beta1 integrin function: confirmed, new and revised roles for a crucial family of cell adhesion molecules J. Cell Sci., January 12, 1997; 110(23): 2895 - 2904. [Abstract] [PDF]

				M. Laser, C. D. Willey, W. Jiang, G. Cooper IV, D. R. Menick, M. R. Zile, and D. Kuppuswamy Integrin Activation and Focal Complex Formation in Cardiac Hypertrophy J. Biol. Chem., November 3, 2000; 275(45): 35624 - 35630. [Abstract] [Full Text] [PDF]