Browse by author
Lookup NU author(s): Dr Steven Laval, Emerita Professor Katherine Bushby
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
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. © The Author 2005. Published by Oxford University Press. All rights reserved.
Author(s): Hernandez-Deviez DJ, Martin S, Laval SH, Lo HP, Cooper ST, North KN, Bushby K, Parton RG
Publication type: Article
Publication status: Published
Journal: Human Molecular Genetics
Year: 2006
Volume: 15
Issue: 1
Pages: 129-142
ISSN (print): 0964-6906
ISSN (electronic): 1460-2083
Publisher: Oxford University Press
URL: http://dx.doi.org/10.1093/hmg/ddi434
DOI: 10.1093/hmg/ddi434
PubMed id: 16319126
Altmetrics provided by Altmetric