Biochemical evidence for association of dystrobrevin with the sarcoglycan-sarcospan complex as a basis for understanding sarcoglycanopathy.

Abstract

The sarcoglycan complex is composed of four membrane-spanning dystrophin-associated proteins (DAPs) and is essential for skeletal muscle survival, since the absence or markedly reduced expression of this complex due to mutation of any one of the sarcoglycan genes causes a group of muscular dystrophies, collectively termed sarcoglycanopathy. Although one of the putative functions of the sarcoglycan complex is its participation in signaling processes, detailed studies have been scarce. Very recently, it was shown that gene knockout mice for a DAP, alpha-dystrobrevin, exhibit a dystrophic phenotype, possibly due to defects in muscle cell signaling. To clarify the putative function of the sarcoglycan complex, it is essential to determine whether or not there is a link between it and the intracellular signaling molecules. To elucidate this, we developed new methods for preparing various DAP complexes containing the sarcoglycan complex from the purified dystrophin-DAP complex. It was suggested from one of the complexes prepared that the sarco-glycan-sarcospan complex (the sarcoglycan complex associated with sarcospan) is associated with syntrophin and/or dystrobrevin. Further analysis of this complex revealed that the N-terminal half of dystrobrevin participates in this association. It is thus considered that the sarcoglycan-sarcospan complex is linked to the signaling protein neuronal nitric oxide synthase via alpha-syntrophin associated with dystrobrevin.

• Authors: M Yoshida, H Hama, M Ishikawa-Sakurai, M Imamura, Y Mizuno, K Araishi, E Wakabayashi-Takai, S Noguchi, T Sasaoka, E Ozawa
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 9 Issue 7 Pg. 1033-40 (Apr 12 2000) ISSN: 0964-6906 [Print] England
• PMID: 10767327 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Cytoskeletal Proteins
• DAG1 protein, human
• Dystrophin
• Dystrophin-Associated Proteins
• Membrane Glycoproteins
• Membrane Proteins
• Neoplasm Proteins
• Sspn protein, mouse
• dystrobrevin
• Dystroglycans
• Calpain

Topics

• Animals
• Calpain (metabolism)
• Carrier Proteins (metabolism)
• Chromatography, Gel
• Cytoskeletal Proteins (biosynthesis, genetics, metabolism)
• Dystroglycans
• Dystrophin (metabolism)
• Dystrophin-Associated Proteins
• Electrophoresis, Polyacrylamide Gel
• Immunohistochemistry
• Membrane Glycoproteins (genetics, metabolism)
• Membrane Proteins (biosynthesis, metabolism)
• Mice
• Mice, Knockout
• Models, Biological
• Muscles (metabolism)
• Muscular Dystrophies (metabolism)
• Neoplasm Proteins
• Precipitin Tests
• Protein Binding