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Characterisation of alpha-dystrobrevin in muscle.

Dystrophin-related and associated proteins are important for the formation and maintenance of the mammalian neuromuscular junction. Initial studies in the electric organ of Torpedo californica showed that the dystrophin-related protein dystrobrevin (87K) co-purifies with the acetylcholine receptors and other postsynaptic proteins. Dystrobrevin is also a major phosphotyrosine-containing protein in the postsynaptic membrane. Since inhibitors of tyrosine protein phosphorylation block acetylcholine receptor clustering in cultured muscle cells, we examined the role of alpha-dystrobrevin during synapse formation and in response to agrin. Using specific antibodies, we show that C2 myoblasts and early myotubes only produce alpha-dystrobrevin-1, the mammalian orthologue of Torpedo dystrobrevin, whereas mature skeletal muscle expresses three distinct alpha-dystrobrevin isoforms. In myotubes, alpha-dystrobrevin-1 is found on the cell surface and also in acetylcholine receptor-rich domains. Following agrin stimulation, alpha-dystrobrevin-1 becomes re-localised beneath the cell surface into macroclusters that contain acetylcholine receptors and another dystrophin-related protein, utrophin. This redistribution is not associated with tyrosine phosphorylation of alpha-dystrobrevin-1 by agrin. Furthermore, we show that alpha-dystrobrevin-1 is associated with both utrophin in C2 cells and dystrophin in mature skeletal muscle. Thus alpha-dystrobrevin-1 is a component of two protein complexes in muscle, one with utrophin at the neuromuscular junction and the other with dystrophin at the sarcolemma. These results indicate that alpha-dystrobrevin-1 is not involved in the phosphorylation-dependent, early stages of receptor clustering, but rather in the stabilisation and maturation of clusters, possibly via an interaction with utrophin.

Pubmed ID: 9701558

Authors

  • Nawrotzki R
  • Loh NY
  • Ruegg MA
  • Davies KE
  • Blake DJ

Journal

Journal of cell science

Publication Data

September 25, 1998

Associated Grants

  • Agency: Wellcome Trust, Id:

Mesh Terms

  • Agrin
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Brain
  • Cell Line
  • Cytoskeletal Proteins
  • Disease Models, Animal
  • Dystrophin-Associated Proteins
  • Fetus
  • Humans
  • Membrane Proteins
  • Mice
  • Mice, Inbred mdx
  • Molecular Sequence Data
  • Muscle Proteins
  • Muscle, Skeletal
  • Neuropeptides
  • Phosphotyrosine
  • Protein Isoforms
  • Synapses
  • Utrophin
  • Vanadates