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

Newey, S. E., Gramolini, A. O., Wu, J., Holzfeind, P., Jasmin, B. J., Davies, K. 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 alpha-dystrobrevin transcripts in skeletal muscle. Molecular and Cellular Neuroscience 17 (1) , pp. 127-140. 10.1212/01.wnl.0000302174.08951.cf.

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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 > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher:	Elsevier
ISSN:	1044-7431
Last Modified:	31 Oct 2022 09:24
URI:	https://orca.cardiff.ac.uk/id/eprint/80941

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