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PMID: 10995444 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Assembly of the dystrophin-associated protein complex does not require the dystrophin COOH-terminal domain.

The Journal of cell biology ·Vol. 150 ·No. 6 ·2000-09-18 ·Pages 1399-410

Crawford GE, Faulkner JA, Crosbie RH, Campbell KP, Froehner SC, Chamberlain JS

Abstract

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 direct 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.

MeSH Terms
Actins/metabolism Animals Binding Sites/physiology Cell Nucleus/pathology Cytoskeletal Proteins/analysis,metabolism Disease Models, Animal Dystrophin/chemistry,genetics,metabolism Dystrophin-Associated Proteins Exons Membrane Proteins/analysis,metabolism Mice Mice, Inbred C57BL Mice, Inbred mdx Mice, Transgenic Microsomes/chemistry,metabolism Muscle Contraction/genetics Muscle Fibers, Skeletal/chemistry,metabolism,pathology Muscle Proteins/analysis,metabolism Muscular Dystrophies/metabolism,pathology Neuropeptides/analysis,metabolism Protein Structure, Tertiary Utrophin
Chemicals
Actins Cytoskeletal Proteins Dtna protein, mouse Dystrophin Dystrophin-Associated Proteins Membrane Proteins Muscle Proteins Neuropeptides Utrn protein, mouse Utrophin dystrobrevin syntrophin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Crawford G E
Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan 48109-0618, USA.
Faulkner J A
Crosbie R H
Campbell K P
Froehner S C
Chamberlain J S
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.150.6.1399
Published
2000-09-18
Pages
1399-410
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2150715
Subset
IM
Grants
NIAMS NIH HHS · AR40864 · United States
NIA NIH HHS · AG15434 · United States
External Links
PubMed source DOI: 10.1083/jcb.150.6.1399 PMC Full Text View journal details
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