Journal article
Molecular Signatures of Membrane Protein Complexes Underlying Muscular Dystrophy
Molecular & cellular proteomics, Vol.15(6), pp.2169-2185
06/2016
DOI: 10.1074/mcp.M116.059188
PMCID: PMC5083101
PMID: 27099343
Abstract
Mutations in genes encoding components of the sarcolemmal dystrophin-glycoprotein complex (DGC) are responsible for a large number of muscular dystrophies. As such, molecular dissection of the DGC is expected to both reveal pathological mechanisms, and provides a biological framework for validating new DGC components. Establishment of the molecular composition of plasma-membrane protein complexes has been hampered by a lack of suitable biochemical approaches. Here we present an analytical workflow based upon the principles of protein correlation profiling that has enabled us to model the molecular composition of the DGC in mouse skeletal muscle. We also report our analysis of protein complexes in mice harboring mutations in DGC components. Bioinformatic analyses suggested that cell-adhesion pathways were under the transcriptional control of NFκB in DGC mutant mice, which is a finding that is supported by previous studies that showed NFκB-regulated pathways underlie the pathophysiology of DGC-related muscular dystrophies. Moreover, the bioinformatic analyses suggested that inflammatory and compensatory mechanisms were activated in skeletal muscle of DGC mutant mice. Additionally, this proteomic study provides a molecular framework to refine our understanding of the DGC, identification of protein biomarkers of neuromuscular disease, and pharmacological interrogation of the DGC in adult skeletal muscle https://www.mda.org/disease/congenital-muscular-dystrophy/research.
Details
- Title: Subtitle
- Molecular Signatures of Membrane Protein Complexes Underlying Muscular Dystrophy
- Creators
- Rolf Turk - From the ‡Howard Hughes Medical Institute, §Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, ¶Department of Molecular Physiology and Biophysics, ‖Department of Neurology, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IowaJordy J Hsiao - ¶Department of Molecular Physiology and BiophysicsMelinda M Smits - ¶Department of Molecular Physiology and BiophysicsBrandon H Ng - ¶Department of Molecular Physiology and BiophysicsTyler C Pospisil - From the ‡Howard Hughes Medical Institute, §Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, ¶Department of Molecular Physiology and Biophysics, ‖Department of Neurology, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IowaKayla S Jones - From the ‡Howard Hughes Medical Institute, §Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, ¶Department of Molecular Physiology and Biophysics, ‖Department of Neurology, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IowaKevin P Campbell - From the ‡Howard Hughes Medical Institute, §Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, ¶Department of Molecular Physiology and Biophysics, ‖Department of Neurology, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IowaMichael E Wright - ¶Department of Molecular Physiology and Biophysics, michael-e-wright@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Molecular & cellular proteomics, Vol.15(6), pp.2169-2185
- DOI
- 10.1074/mcp.M116.059188
- PMID
- 27099343
- PMCID
- PMC5083101
- NLM abbreviation
- Mol Cell Proteomics
- ISSN
- 1535-9476
- eISSN
- 1535-9484
- Publisher
- United States
- Grant note
- U54 NS053672 / NINDS NIH HHS T32 HL007121 / NHLBI NIH HHS Howard Hughes Medical Institute RC2 NS069521 / NINDS NIH HHS
- Language
- English
- Date published
- 06/2016
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020780402771
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