Dysferlin interacts with annexins A1 and A2 and mediates sarcolemmal wound-healing - PubMed (original) (raw)

. 2003 Dec 12;278(50):50466-73.

doi: 10.1074/jbc.M307247200. Epub 2003 Sep 23.

Affiliations

Free article

Dysferlin interacts with annexins A1 and A2 and mediates sarcolemmal wound-healing

Niall J Lennon et al. J Biol Chem. 2003.

Free article

Abstract

Mutations in the dysferlin gene cause limb girdle muscular dystrophy type 2B and Miyoshi myopathy. We report here the results of expression profile analyses and in vitro investigations that point to an interaction between dysferlin and the Ca2+ and lipid-binding proteins, annexins A1 and A2, and define a role for dysferlin in Ca2+-dependent repair of sarcolemmal injury through a process of vesicle fusion. Expression profiling identified a network of genes that are co-regulated in dysferlinopathic mice. Co-immunofluorescence, co-immunoprecipitation, and fluorescence lifetime imaging microscopy revealed that dysferlin normally associates with both annexins A1 and A2 in a Ca2+ and membrane injury-dependent manner. The distribution of the annexins and the efficiency of sarcolemmal wound-healing are significantly disrupted in dysferlin-deficient muscle. We propose a model of muscle membrane healing mediated by dysferlin that is relevant to both normal and dystrophic muscle and defines the annexins as potential muscular dystrophy genes.

PubMed Disclaimer

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources