Mutations in genes encoding for the sarcoglycans, a subset of proteins within the dystrophin–glycoprotein complex, produce a limb-girdle muscular dystrophy phenotype; however, the precise role of this group of proteins in the skeletal muscle is not known. To understand the role of the sarcoglycan complex, we looked for sarcoglycan interacting proteins with the hope of finding novel members of the dystrophin–glycoprotein complex. Using the yeast two-hybrid method, we have identified a skeletal muscle-specific form of filamin, which we term filamin 2 (FLN2), as a γ- and δ-sarcoglycan interacting protein. In addition, we demonstrate that FLN2 protein localization in limb-girdle muscular dystrophy and Duchenne muscular dystrophy patients and mice is altered when compared with unaffected individuals. Previous studies of filamin family members have determined that these proteins are involved in actin reorganization and signal transduction cascades associated with cell migration, adhesion, differentiation, force transduction, and survival. Specifically, filamin proteins have been found essential in maintaining membrane integrity during force application. The finding that FLN2 interacts with the sarcoglycans introduces new implications for the pathogenesis of muscular dystrophy.
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10 January 2000
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January 10 2000
Filamin 2 (FLN2): A Muscle-specific Sarcoglycan Interacting Protein
Terri G. Thompson,
Terri G. Thompson
*Howard Hughes Medical Institute and Division of Genetics, Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115;
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Yiu-Mo Chan,
Yiu-Mo Chan
*Howard Hughes Medical Institute and Division of Genetics, Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115;
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Andrew A. Hack,
Andrew A. Hack
‡Department of Molecular Genetics and Cell Biology,
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Melissa Brosius,
Melissa Brosius
*Howard Hughes Medical Institute and Division of Genetics, Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115;
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Michael Rajala,
Michael Rajala
*Howard Hughes Medical Institute and Division of Genetics, Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115;
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Hart G.W. Lidov,
Hart G.W. Lidov
*Howard Hughes Medical Institute and Division of Genetics, Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115;
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Elizabeth M. McNally,
Elizabeth M. McNally
‡Department of Molecular Genetics and Cell Biology,
§Department of Medicine, Section of Cardiology, University of Chicago, Chicago, Illinois 60637; and
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Simon Watkins,
Simon Watkins
||Center for Biological Imaging, University of Pittsburgh, Pittsburgh, Pennsylvania 15261
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Louis M. Kunkel
*Howard Hughes Medical Institute and Division of Genetics, Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115;
Address correspondence to Louis M. Kunkel, Ph.D., Howard Hughes Medical Institute, Division of Genetics, Enders 570, Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115. Tel.: (617) 355-7576. Fax: (617) 355-7588. E-mail: [email protected]
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Terri G. Thompson
*Howard Hughes Medical Institute and Division of Genetics, Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115;
Yiu-Mo Chan
*Howard Hughes Medical Institute and Division of Genetics, Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115;
Andrew A. Hack
‡Department of Molecular Genetics and Cell Biology,
Melissa Brosius
*Howard Hughes Medical Institute and Division of Genetics, Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115;
Michael Rajala
*Howard Hughes Medical Institute and Division of Genetics, Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115;
Hart G.W. Lidov
*Howard Hughes Medical Institute and Division of Genetics, Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115;
Elizabeth M. McNally
‡Department of Molecular Genetics and Cell Biology,
§Department of Medicine, Section of Cardiology, University of Chicago, Chicago, Illinois 60637; and
Simon Watkins
||Center for Biological Imaging, University of Pittsburgh, Pittsburgh, Pennsylvania 15261
Address correspondence to Louis M. Kunkel, Ph.D., Howard Hughes Medical Institute, Division of Genetics, Enders 570, Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115. Tel.: (617) 355-7576. Fax: (617) 355-7588. E-mail: [email protected]
1
Abbreviations used in this paper: CoIP, coimmunoprecipitate; DGC, dystrophin–glycoprotein complex; DMD, Duchenne muscular dystrophy; ECM, extracellular matrix; EST, expressed sequence tag; IMF, immunofluorescence; FLN2, filamin 2; GP, glycoprotein; LGMD, limb-girdle muscular dystrophy.
Received:
April 13 1999
Revision Received:
November 04 1999
Accepted:
November 23 1999
Online ISSN: 1540-8140
Print ISSN: 0021-9525
© 2000 The Rockefeller University Press
2000
J Cell Biol (2000) 148 (1): 115–126.
Article history
Received:
April 13 1999
Revision Received:
November 04 1999
Accepted:
November 23 1999
Citation
Terri G. Thompson, Yiu-Mo Chan, Andrew A. Hack, Melissa Brosius, Michael Rajala, Hart G.W. Lidov, Elizabeth M. McNally, Simon Watkins, Louis M. Kunkel; Filamin 2 (FLN2): A Muscle-specific Sarcoglycan Interacting Protein. J Cell Biol 10 January 2000; 148 (1): 115–126. doi: https://doi.org/10.1083/jcb.148.1.115
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