期刊
JOURNAL OF CELL BIOLOGY
卷 150, 期 6, 页码 1399-1409出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.150.6.1399
关键词
dystrophin; muscular dystrophy; syntrophin; dystrobrevin; mdx mice
类别
资金
- NIAMS NIH HHS [AR40864, R01 AR040864, R37 AR040864] Funding Source: Medline
- NIA NIH HHS [P01 AG015434, AG15434] Funding Source: Medline
Dystrophin is a multidomain protein that links the actin cytoskeleton to laminin in the extracellular matrix through the dystrophin associated protein (DAP) complex. The COOH-terminal domain of dystrophin binds to two components of the DAP complex, syntrophin and dystrobrevin. To understand the role of syntrophin and dystrobrevin, we previously generated a series of transgenic mouse lines expressing dystrophins with deletions throughout the COOH-terminal domain. Each of these mice had normal muscle function and displayed normal localization of syntrophin and dystrobrevin, Since syntrophin and dystrobrevin bind to each other as well as to dystrophin, we have now generated a transgenic mouse deleted for the entire dystrophin COOH-terminal domain. Unexpectedly, this truncated dystrophin supported normal muscle function and assembly of the DAP complex. These results demonstrate that syntrophin and dystrobrevin functionally associate with the DAP complex in the absence of a di;ect link to dystrophin. We also observed that the DAP complexes in these different transgenic mouse strains were not identical. Instead, the DAP complexes contained varying ratios of syntrophin and dystrobrevin isoforms. These results suggest that alternative splicing of the dystrophin gene, which naturally generates COOH-terminal deletions in dystrophin, may function to regulate the isoform composition of the DAP complex.
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