A novel mechanism for modulating synaptic gene expression: differential localization of α-dystrobrevin transcripts in skeletal muscle

Newey, Sarah E., Gramolini, Anthony O., Wu, Jun, Holzfiend, Paul, Jasmin, Bernard J., Davies, Kay E. and Blake, Derek J. ORCID: https://orcid.org/0000-0002-5005-4731 2001. A novel mechanism for modulating synaptic gene expression: differential localization of α-dystrobrevin transcripts in skeletal muscle. Molecular and Cellular Neuroscience 17 (1) , pp. 127-140. 10.1006/mcne.2000.0918

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Abstract

α-Dystrobrevin is a dystrophin-related and -associated protein that is involved in synapse maturation and is required for normal muscle function. There are three protein isoforms in skeletal muscle, α-dystrobrevin-1, -2, and -3 that are encoded by the single α-dystrobrevin gene. To understand the role of these proteins in muscle we have investigated the localisation and transcript distribution of the different α-dystrobrevin isoforms. α-Dystrobrevin-1 and -2 are concentrated at the neuromuscular junction and are both recruited into agrin-induced acetylcholine receptor clusters in cultured myotubes. We also demonstrate that all α-dystrobrevin mRNAs are transcribed from a single promoter in skeletal muscle. However, only transcripts encoding α-dystrobrevin-1 are preferentially accumulated at postsynaptic sites. These data suggest that the synaptic accumulation of α-dystrobrevin-1 mRNA occurs posttranscriptionally, identifying a novel mechanism for synaptic gene expression. Taken together, these results indicate that different isoforms possess distinct roles in synapse formation and possibly in the pathogenesis of muscular dystrophy.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects:	R Medicine > R Medicine (General)
Publisher:	Elsevier
ISSN:	1044-7431
Last Modified:	24 Oct 2022 11:46
URI:	https://orca.cardiff.ac.uk/id/eprint/49257

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