The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal muscle

Dysferlin is a surface membrane protein in skeletal muscle whose deficiency causes distal and proximal, recessively inherited, forms of muscular dystrophy designated Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B), respectively. The function of dysferlin is not defined. Cav...

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Bibliographic Details
Published in:Human molecular genetics 2001-08, Vol.10 (17), p.1761-1766
Main Authors: MATSUDA, Chie, HAYASHI, Yukiko K, OGAWA, Megumu, AOKI, Masashi, MURAYAMA, Kumiko, NISHINO, Ichizo, NONAKA, Ikuya, ARAHATA, Kiichi, BROWN, Robert H
Format: Article
Language:English
Subjects:
Biological and medical sciences
CAV3 gene
Caveolin 3
Caveolins - metabolism
Dysferlin
Fundamental and applied biological sciences. Psychology
Humans
Immunohistochemistry
limb-girdle muscular dystrophy
Membrane Proteins
Miyoshi myopathy
Molecular and cellular biology
Muscle Proteins - metabolism
Muscles - metabolism
Muscles - ultrastructure
Muscular Dystrophies - genetics
Muscular Dystrophies - metabolism
Muscular Dystrophies - pathology
Mutation, Missense
Sarcolemma - pathology
Sarcolemma - ultrastructure
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Summary:Dysferlin is a surface membrane protein in skeletal muscle whose deficiency causes distal and proximal, recessively inherited, forms of muscular dystrophy designated Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B), respectively. The function of dysferlin is not defined. Caveolin-3 is another skeletal muscle membrane protein which is important in the formation of caveolae and whose mutations cause dominantly inherited limb girdle muscular dystrophy type 1C (LGMD1C). We report that dysferlin co-immunoprecipitates with caveolin-3 from biopsied normal human skeletal muscles. We also describe abnormal localization of dysferlin in muscles from patients with LGMD1C including novel missense mutation (T64P) in the human caveolin-3 gene (CAV3). The immunoprecipitation data are consistent with the parallel observation that dysferlin immunostaining is not normal in LGMD1C muscles. Amino acid sequence analysis of the dysferlin protein reveals seven sites that correspond to caveolin-3 scaffold-binding motifs, and one site that is a potential target to bind the WW domain of the caveolin-3 protein. This is the first description of a possible dysferlin interacting protein; it suggests the hypothesis that one function of dysferlin may be to interact with caveolin-3 to subserve signaling functions of caveolae.
ISSN:0964-6906
1460-2083
1460-2083
DOI:10.1093/hmg/10.17.1761