Journal article
Forced expression of dystrophin deletion constructs reveals structure-function correlations
The Journal of cell biology, Vol.134(1), pp.93-102
07/1996
DOI: 10.1083/jcb.134.1.93
PMCID: PMC2120912
PMID: 8698825
Abstract
Dystrophin plays an important role in skeletal muscle by linking the cytoskeleton and the extracellular matrix. The amino terminus of dystrophin binds to actin and possibly other components of the subsarcolemmal cytoskeleton, while the carboxy terminus associates with a group of integral and peripheral membrane proteins and glycoproteins that are collectively known as the dystrophin-associated protein (DAP) complex. We have generated transgenic/mdx mice expressing "full-length" dystrophin constructs, but with consecutive deletions within the COOH-terminal domains. These mice have enabled analysis of the interaction between dystrophin and members of the DAP complex and the effects that perturbing these associations have on the dystrophic process. Deletions within the cysteine-rich region disrupt the interaction between dystrophin and the DAP complex, leading to a severe dystrophic pathology. These deletions remove the beta-dystroglycan-binding site, which leads to a parallel loss of both beta-dystroglycan and the sarcoglycan complex from the sarcolemma. In contrast, deletion of the alternatively spliced domain and the extreme COOH terminus has no apparent effect on the function of dystrophin when expressed at normal levels. The proteins resulting from these latter two deletions supported formation of a completely normal DAP complex, and their expression was associated with normal muscle morphology in mdx mice. These data indicate that the cysteine-rich domain is critical for functional activity, presumably by mediating a direct interaction with beta-dystroglycan. However, the remainder of the COOH terminus is not required for assembly of the DAP complex.
Details
- Title: Subtitle
- Forced expression of dystrophin deletion constructs reveals structure-function correlations
- Creators
- Jill A Rafael - Department of Human Genetics, University of Michigan Medical School, Ann Arbor, 48109, USAGregory A CoxKathleen CorradoDaniel JungKevin P CampbellJeffrey S Chamberlain
- Resource Type
- Journal article
- Publication Details
- The Journal of cell biology, Vol.134(1), pp.93-102
- Publisher
- United States
- DOI
- 10.1083/jcb.134.1.93
- PMID
- 8698825
- PMCID
- PMC2120912
- ISSN
- 0021-9525
- eISSN
- 1540-8140
- Grant note
- AR40864 / NIAMS NIH HHS
- Language
- English
- Date published
- 07/1996
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984068269002771
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