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Interactions between dystrophin and the sarcolemma membrane.

Publication ,  Journal Article
Chamberlain, JS; Corrado, K; Rafael, JA; Cox, GA; Hauser, M; Lumeng, C
Published in: Soc Gen Physiol Ser
1997

Dystrophin serves as a link between the subsarcolemmal cytoskeleton and the extracellular matrix. The NH2 terminus attaches to the cytoskeleton, while the COOH terminus attaches to the dystrophin associated protein (DAP) complex, which can be separated into the dystroglycan, sarcoglycan, and syntrophin subcomplexes. While the function of each DAP is not known, the dystroglycan complex binds laminin in the extracellular matrix, and binds the dystrophin COOH terminus in vitro. The syntrophins also bind the dystrophin COOH terminus in vitro, but no evidence has been reported for an interaction between dystrophin and the sarcoglycans. Human mutations have been found in dystrophin, the sarcoglycans and laminin, all of which lead to various types of muscular dystrophy. We have been studying the dystrophin domains necessary for formation of a functional complex by generating transgenic mdx (dystrophin minus) mice expressing internally truncated dystrophins. These mice provide in vivo models to study the localization of truncated dystrophin isoforms, the association of the truncated proteins with the DAP complex, and the functional capacity of the assembled DAP complexes. Expression of a dystrophin deleted for most of the NH2-terminal domain in mdx mice leads to only a mild dystrophy, indicating that dystrophin can attach to the cytoskeleton by multiple mechanisms. Truncation of the central rod domain leads to normal DAP complex formation and almost fully prevents development of dystrophy. Deletion analysis of the COOH-terminal regions indicates that a broad cysteine-rich domain is indispensable for dystrophin function. This region coincides with the in vitro identified beta-dystroglycan binding domain. Mice lacking this latter domain express very low levels of the sarcoglycans, indicating that the sarcoglycan complex binds dystrophin via dystroglycan. All deletion constructs tested lead to normal expression of the syntrophins, indicating that syntrophin associates with the DAP complex via multiple binding partners.

Duke Scholars

Published In

Soc Gen Physiol Ser

ISSN

0094-7733

Publication Date

1997

Volume

52

Start / End Page

19 / 29

Location

United States

Related Subject Headings

  • Sarcolemma
  • Mutagenesis
  • Muscle Proteins
  • Mice, Transgenic
  • Mice, Inbred mdx
  • Mice, Inbred C57BL
  • Mice
  • Membrane Proteins
  • Membrane Glycoproteins
  • Gene Expression
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chamberlain, J. S., Corrado, K., Rafael, J. A., Cox, G. A., Hauser, M., & Lumeng, C. (1997). Interactions between dystrophin and the sarcolemma membrane. Soc Gen Physiol Ser, 52, 19–29.
Chamberlain, J. S., K. Corrado, J. A. Rafael, G. A. Cox, M. Hauser, and C. Lumeng. “Interactions between dystrophin and the sarcolemma membrane.Soc Gen Physiol Ser 52 (1997): 19–29.
Chamberlain JS, Corrado K, Rafael JA, Cox GA, Hauser M, Lumeng C. Interactions between dystrophin and the sarcolemma membrane. Soc Gen Physiol Ser. 1997;52:19–29.
Chamberlain, J. S., et al. “Interactions between dystrophin and the sarcolemma membrane.Soc Gen Physiol Ser, vol. 52, 1997, pp. 19–29.
Chamberlain JS, Corrado K, Rafael JA, Cox GA, Hauser M, Lumeng C. Interactions between dystrophin and the sarcolemma membrane. Soc Gen Physiol Ser. 1997;52:19–29.

Published In

Soc Gen Physiol Ser

ISSN

0094-7733

Publication Date

1997

Volume

52

Start / End Page

19 / 29

Location

United States

Related Subject Headings

  • Sarcolemma
  • Mutagenesis
  • Muscle Proteins
  • Mice, Transgenic
  • Mice, Inbred mdx
  • Mice, Inbred C57BL
  • Mice
  • Membrane Proteins
  • Membrane Glycoproteins
  • Gene Expression