Characterisation of alpha-dystrobrevin in muscle

Nawrotzki, Ralph, Loh, Nellie Y., Ruegg, M. A., Davies, Kay E. and Blake, Derek J. ORCID: https://orcid.org/0000-0002-5005-4731 1998. Characterisation of alpha-dystrobrevin in muscle. Journal of Cell Science 111 (17) , pp. 2595-2605.

Full text not available from this repository.

Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	dystrobrevin, utrophin, agrin, acetylcholine receptor (AChR) clustering, muscle
Publisher:	The Company of Biologists
ISSN:	0021-9533
Related URLs:	Publisher
Last Modified:	24 Oct 2022 11:49
URI:	https://orca.cardiff.ac.uk/id/eprint/49419

Citation Data

Cited 83 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item