QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 13 July 2004
doi: 10.1242/jcs.01234

This Article Figures Only Full Text Full Text (PDF) Movie All Versions of this Article: jcs.01234v1 117/17/3821    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Allikian, M. J. Articles by McNally, E. M. Search for Related Content PubMed PubMed Citation Articles by Allikian, M. J. Articles by McNally, E. M. Social Bookmarking                         What's this?

Genetic compensation for sarcoglycan loss by integrin 7ß1 in muscle

¹ Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA
² Department of Human Genetics, The University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA
³ Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester, M13 9PT, UK

^* Author for correspondence (e-mail: emcnally{at}medicine.bsd.uchicago.edu)

Accepted 23 March 2004

Disruption of the sarcoglycan complex leads to muscle membrane instability and muscular dystrophy in humans and mice. Through the dystrophin glycoprotein complex, sarcoglycan participates in connecting the internal cytoskeleton to the membrane and the extracellular matrix. Integrin 7ß1 is also a transmembrane protein of skeletal and cardiac muscle that similarly links the cytoskeleton to the extracellular matrix. Mice lacking integrin 7 develop mild muscle degeneration, while sarcoglycan mutant mice display overt muscle degeneration and muscular dystrophy. In sarcoglycan-deficient muscle, integrin 7 protein was upregulated at the plasma membrane. To ascertain whether integrin 7 upregulation compensates for the loss of the transmembrane sarcoglycan linkage in sarcoglycan-deficient muscle, we generated mice lacking both integrin 7 and -sarcoglycan (gxi). These double-mutant gxi mice exhibit profound, rapid muscle degeneration leading to death before one month of age consistent with a weakened cellular attachment to the extracellular matrix. The regenerative capacity of gxi muscle was intact with increased embryonic myosin heavy chain expression, myofiber central nucleation and normal in vivo myoblast differentiation. Therefore, upregulation of integrin 7ß1 compensates as a transmembrane muscle cell attachment for sarcoglycan consistent with overlapping roles for sarcoglycan and integrins in mediating cytoskeletal-membrane-extracellular matrix interaction.

Key words: Sarcoglycan, Dystrophin, Integrin, Membrane, Muscle

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. Kanagawa, A. Nishimoto, T. Chiyonobu, S. Takeda, Y. Miyagoe-Suzuki, F. Wang, N. Fujikake, M. Taniguchi, Z. Lu, M. Tachikawa, et al. Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy Hum. Mol. Genet., February 15, 2009; 18(4): 621 - 631. [Abstract] [Full Text] [PDF]

				J. E. Rooney, P. B. Gurpur, Z. Yablonka-Reuveni, and D. J. Burkin Laminin-111 Restores Regenerative Capacity in a Mouse Model for {alpha}7 Integrin Congenital Myopathy Am. J. Pathol., January 1, 2009; 174(1): 256 - 264. [Abstract] [Full Text] [PDF]

				J. Liu, D. J. Burkin, and S. J. Kaufman Increasing {alpha}7{beta}1-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression Am J Physiol Cell Physiol, February 1, 2008; 294(2): C627 - C640. [Abstract] [Full Text] [PDF]

				P. Sharma, T. Tran, G. L. Stelmack, K. McNeill, R. Gosens, M. M. Mutawe, H. Unruh, W. T. Gerthoffer, and A. J. Halayko Expression of the dystrophin-glycoprotein complex is a marker for human airway smooth muscle phenotype maturation Am J Physiol Lung Cell Mol Physiol, January 1, 2008; 294(1): L57 - L68. [Abstract] [Full Text] [PDF]

				A. L. Gheyara, A. Vallejo-Illarramendi, K. Zang, L. Mei, R. St.-Arnaud, S. Dedhar, and L. F. Reichardt Deletion of Integrin-Linked Kinase from Skeletal Muscles of Mice Resembles Muscular Dystrophy Due to {alpha}7 1-Integrin Deficiency Am. J. Pathol., December 1, 2007; 171(6): 1966 - 1977. [Abstract] [Full Text] [PDF]

				W. W. Dye, R. L. Gleason, E. Wilson, and J. D. Humphrey Altered biomechanical properties of carotid arteries in two mouse models of muscular dystrophy J Appl Physiol, August 1, 2007; 103(2): 664 - 672. [Abstract] [Full Text] [PDF]

				D. J. Milner and S. J. Kaufman {alpha}7{beta}1 Integrin Does Not Alleviate Disease in a Mouse Model of Limb Girdle Muscular Dystrophy Type 2F Am. J. Pathol., February 1, 2007; 170(2): 609 - 619. [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]

				X. Shi and D. J. Garry Muscle stem cells in development, regeneration, and disease. Genes & Dev., July 1, 2006; 20(13): 1692 - 1708. [Abstract] [Full Text] [PDF]

				J. E. Rooney, J. V. Welser, M. A. Dechert, N. L. Flintoff-Dye, S. J. Kaufman, and D. J. Burkin Severe muscular dystrophy in mice that lack dystrophin and {alpha}7 integrin J. Cell Sci., June 1, 2006; 119(11): 2185 - 2195. [Abstract] [Full Text] [PDF]

				M. D. Boppart, D. J. Burkin, and S. J. Kaufman {alpha}7beta1-Integrin regulates mechanotransduction and prevents skeletal muscle injury Am J Physiol Cell Physiol, June 1, 2006; 290(6): C1660 - C1665. [Abstract] [Full Text] [PDF]

				J.-T. Chao, L. A. Martinez-Lemus, S. J. Kaufman, G. A. Meininger, K. S. Ramos, and E. Wilson Modulation of {alpha}7-integrin-mediated adhesion and expression by platelet-derived growth factor in vascular smooth muscle cells Am J Physiol Cell Physiol, April 1, 2006; 290(4): C972 - C980. [Abstract] [Full Text] [PDF]

				F. Riuzzi, G. Sorci, and R. Donato The Amphoterin (HMGB1)/Receptor for Advanced Glycation End Products (RAGE) Pair Modulates Myoblast Proliferation, Apoptosis, Adhesiveness, Migration, and Invasiveness: FUNCTIONAL INACTIVATION OF RAGE IN L6 MYOBLASTS RESULTS IN TUMOR FORMATION IN VIVO J. Biol. Chem., March 24, 2006; 281(12): 8242 - 8253. [Abstract] [Full Text] [PDF]

				C. Guo, M. Willem, A. Werner, G. Raivich, M. Emerson, L. Neyses, and U. Mayer Absence of {alpha}7 integrin in dystrophin-deficient mice causes a myopathy similar to Duchenne muscular dystrophy Hum. Mol. Genet., March 15, 2006; 15(6): 989 - 998. [Abstract] [Full Text] [PDF]

				T. A. H. Jarvinen, T. L. N. Jarvinen, M. Kaariainen, H. Kalimo, and M. Jarvinen Muscle Injuries: Biology and Treatment Am. J. Sports Med., May 1, 2005; 33(5): 745 - 764. [Abstract] [Full Text] [PDF]