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Aberrant dysferlin trafficking in cells lacking caveolin or expressing dystrophy mutants of caveolin-3
Hernandez-Deviez, D. J., Martin, S., Laval, S. H., Lo, H. P., Cooper, S. T., North, K. N., Bushby, K. and Parton, RG (2006) Aberrant dysferlin trafficking in cells lacking caveolin or expressing dystrophy mutants of caveolin-3. Human Molecular Genetics, 15 1: 129-142.
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| Author(s) |
Hernandez-Deviez, D. J.
Martin, S.
Laval, S. H.
Lo, H. P.
Cooper, S. T.
North, K. N.
Bushby, K.
Parton, RG
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| Title |
Aberrant dysferlin trafficking in cells lacking caveolin or expressing dystrophy mutants of caveolin-3
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| Journal name |
Human Molecular Genetics
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| Publication date |
2006
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| Volume number |
15
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| Issue number |
1
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| ISSN |
0964-6906
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| Start page |
129
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| End page |
142
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| Total pages |
14
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| Place of publication |
Oxford
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| Publisher |
Oxford Univ Press
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| Abstract |
Mutations in the dysferlin (DYSF) and caveolin-3 (CAV3) genes are associated with muscle disease. Dysferlin is mislocalized, by an unknown mechanism, in muscle from patients with mutations in caveolin-3 (Cav-3). To examine the link between Cav-3 mutations and dysferlin mistargeting, we studied their localization at high resolution in muscle fibers, in a model muscle cell line, and upon heterologous expression of dysferlin in muscle cell lines and in wild-type or caveolin-null fibroblasts. Dysferlin shows only partial overlap with Cav-3 on the surface of isolated muscle fibers but co-localizes with Cav-3 in developing transverse (T)-tubules in muscle cell lines. Heterologously expressed dystrophy-associated mutant Cav3R26Q accumulates in the Golgi complex of muscle cell lines or fibroblasts. Cav3R26Q and other Golgi-associated mutants of both Cav-3 (Cav3P104L) and Cav-1 (Cav1P132L) caused a dramatic redistribution of dysferlin to the Golgi complex. Heterologously expressed epitope-tagged dysferlin associates with the plasma membrane in primary fibroblasts and muscle cells. Transport to the cell surface is impaired in the absence of Cav-1 or Cav-3 showing that caveolins are essential for dysferlin association with the PM. These results suggest a functional role for caveolins in a novel post-Golgi trafficking pathway followed by dysferlin.
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| Keyword(s) |
Biochemistry & Molecular Biology
Genetics & Heredity
Girdle Muscular-dystrophy
Rippling Muscle Disease
Developing T-tubules
Plasma-membrane
Skeletal-muscle
Golgi-complex
Cav3 Gene
Fer-1-like Protein
Miyoshi Myopathy
Null Mice
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