The laminin-binding activity of the alpha 7 integrin receptor is defined by developmentally regulated splicing in the extracellular domain [In Process Citation]

BL Ziober, Y Chen and RH Kramer

Department of Stomatology, University of California, San Francisco 94143-0512, USA.

The expression pattern of the laminin-binding alpha 7 beta 1 integrin is developmentally regulated in skeletal, cardiac, and smooth muscle. The X1/X2 alternative splicing in the extracellular domain of alpha 7 is found in the variable region between conserved alpha-chain homology repeat domains III and IV, a site implicated in ligand binding. To assess differences in X1/X2 isoform activity, we generated MCF-7 cell lines transfected with alpha 7-X1/X2 cDNAs. Transfectants expressing the alpha 7-X2 variant adhered rapidly to laminin 1, whereas those expressing alpha 7-X1 failed to attach. That alpha 7-X1 exists in an inactive state was established in assays using an activating beta 1 antibody that induced X1-dependent cell adhesion and spreading. Furthermore, the activation of alpha 7-X1 was cell type specific, and when expressed in HT1080 cells, the integrin was converted into a fully functional receptor capable of promoting adhesion. Thus, the expression of the alpha 7-X1/X2 integrin is a novel mechanism that regulates receptor affinity states in a cell-specific context and may modulate integrin-dependent events during muscle development and repair.

Volume 8, Issue 9, pp. 1723-1734, 09/01/1997
Copyright © 1997 by The American Society for Cell Biology

This article has been cited by other articles:

				T. Samson, C. Will, A. Knoblauch, L. Sharek, K. von der Mark, K. Burridge, and V. Wixler Def-6, a Guanine Nucleotide Exchange Factor for Rac1, Interacts with the Skeletal Muscle Integrin Chain {alpha}7A and Influences Myoblast Differentiation J. Biol. Chem., May 25, 2007; 282(21): 15730 - 15742. [Abstract] [Full Text] [PDF]

				M.-G. Yeh, B. L. Ziober, B. Liu, G. Lipkina, I. S. Vizirianakis, and R. H. Kramer The {beta}1 Cytoplasmic Domain Regulates the Laminin-binding Specificity of the {alpha}7X1 Integrin Mol. Biol. Cell, September 1, 2003; 14(9): 3507 - 3518. [Abstract] [Full Text] [PDF]

				U. Mayer Integrins: Redundant or Important Players in Skeletal Muscle? J. Biol. Chem., April 18, 2003; 278(17): 14587 - 14590. [Full Text] [PDF]

				W. Guan, M. A. Puthenveedu, and M. L. Condic Sensory Neuron Subtypes Have Unique Substratum Preference and Receptor Expression before Target Innervation J. Neurosci., March 1, 2003; 23(5): 1781 - 1791. [Abstract] [Full Text] [PDF]

				A. Rosbottom, C. L. Scudamore, H. von der Mark, E. M. Thornton, S. H. Wright, and H. R. P. Miller TGF-{beta}1 Regulates Adhesion of Mucosal Mast Cell Homologues to Laminin-1 Through Expression of Integrin {alpha}7 J. Immunol., November 15, 2002; 169(10): 5689 - 5695. [Abstract] [Full Text] [PDF]

				M. Kaariainen, L. Nissinen, S. Kaufman, A. Sonnenberg, M. Jarvinen, J. Heino, and H. Kalimo Expression of {alpha}7{beta}1 Integrin Splicing Variants during Skeletal Muscle Regeneration Am. J. Pathol., September 1, 2002; 161(3): 1023 - 1031. [Abstract] [Full Text] [PDF]

				E. Pegoraro, F. Cepollaro, P. Prandini, A. Marin, M. Fanin, C. P. Trevisan, A. H. El-Messlemani, G. Tarone, E. Engvall, E. P. Hoffman, et al. Integrin {alpha}7{beta}1 in Muscular Dystrophy/Myopathy of Unknown Etiology Am. J. Pathol., June 1, 2002; 160(6): 2135 - 2143. [Abstract] [Full Text] [PDF]

				H. von der Mark, I. Williams, O. Wendler, L. Sorokin, K. von der Mark, and E. Poschl Alternative Splice Variants of alpha 7beta 1 Integrin Selectively Recognize Different Laminin Isoforms J. Biol. Chem., February 15, 2002; 277(8): 6012 - 6016. [Abstract] [Full Text] [PDF]

				T. Velling, M. Kusche-Gullberg, T. Sejersen, and D. Gullberg cDNA Cloning and Chromosomal Localization of Human alpha 11 Integrin. A COLLAGEN-BINDING, I DOMAIN-CONTAINING, beta 1-ASSOCIATED INTEGRIN alpha -CHAIN PRESENT IN MUSCLE TISSUES J. Biol. Chem., September 3, 1999; 274(36): 25735 - 25742. [Abstract] [Full Text] [PDF]

				B. L. Ziober, Y. Q. Chen, D. M. Ramos, N. Waleh, and R. H. Kramer Expression of the {{alpha}}7{beta}1 Laminin Receptor Suppresses Melanoma Growth and Metastatic Potential Cell Growth Differ., July 1, 1999; 10(7): 479 - 490. [Abstract] [Full Text]

				M.S. Chen, E.A.C. Almeida, A.-P.J. Huovila, Y. Takahashi, L.M. Shaw, A.M. Mercurio, and J.M. White Evidence that Distinct States of the Integrin alpha 6beta 1 Interact with Laminin and an ADAM J. Cell Biol., February 8, 1999; 144(3): 549 - 561. [Abstract] [Full Text] [PDF]

				M. W. Graner, T. A. Bunch, S. Baumgartner, A. Kerschen, and D. L. Brower Splice Variants of the Drosophila PS2 Integrins Differentially Interact with RGD-containing Fragments of the Extracellular Proteins Tiggrin, Ten-m, and D-Laminin alpha 2 J. Biol. Chem., July 17, 1998; 273(29): 18235 - 18241. [Abstract] [Full Text] [PDF]

				D. Mielenz, S. Hapke, E. Poschl, H. von der Mark, and K. von der Mark The Integrin alpha 7 Cytoplasmic Domain Regulates Cell Migration, Lamellipodia Formation, and p130CAS/Crk Coupling J. Biol. Chem., April 13, 2001; 276(16): 13417 - 13426. [Abstract] [Full Text] [PDF]