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

Journal article

Alpha-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, alpha-dystrobrevin-1, -2, and -3 that are encoded by the single alpha-dystrobrevin gene. To understand the role of these proteins in muscle we have investigated the localisation and transcript distribution of the different alpha-dystrobrevin isoforms. Alpha-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 alpha-dystrobrevin mRNAs are transcribed from a single promoter in skeletal muscle. However, only transcripts encoding alpha-dystrobrevin-1 are preferentially accumulated at postsynaptic sites. These data suggest that the synaptic accumulation of alpha-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.

Authors: Newey, S; Gramolini, A; Wu, J; Holzfeind, P; Jasmin, B

• Publication status: Published
• Journal: Molecular and cellular neurosciences
• Volume: 17
• Issue: 1
• Pages: 127-140
• Publication date: 2001-01-01
• DOI: 10.1006/mcne.2000.0918
• EISSN: 1095-9327
• ISSN: 1044-7431
• Language: English
• Keywords: Receptor Aggregation; Gene Expression Regulation; Cell Line; Mice; Mice, Inbred mdx; Agrin; Protein Isoforms; Muscle, Skeletal; Receptors, Cholinergic; Cytoskeletal Proteins; Dystrophin-Associated Proteins; Membrane Proteins; Mice, Inbred C57BL; Promoter Regions, Genetic; Animals; RNA, Messenger; Synapses