Isoform diversity of dystrobrevin, the murine 87-kDa postsynaptic protein

Blake, Derek J. ORCID: https://orcid.org/0000-0002-5005-4731, Nawrotzki, Ralph A., Peters, Matthew F., Froehner, Stanley C. and Davies, Kay E. 1996. Isoform diversity of dystrobrevin, the murine 87-kDa postsynaptic protein. Journal of Biological Chemistry 271 (13) , pp. 7802-7810. 10.1074/jbc.271.13.7802

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Abstract

Dystrophin-related and -associated proteins are important in the formation and maintenance of the mammalian neuromuscular junction. We have characterized mouse cDNA clones encoding isoforms of the dystrophin-homologous 87-kDa postsynaptic protein, dystrobrevin. In Torpedo, the 87-kDa protein is multiply phosphorylated and closely associated with proteins in the postsynaptic cytoskeleton, including the acetylcholine receptor. In contrast to Torpedo, where only a single transcript is seen, the mouse expresses several mRNAs encoding different isoforms. A 6.0-kilobase transcript in brain encodes a 78-kDa protein (dystrobrevin-1) that is very similar to the Torpedo sequence. A second transcript encodes a 59-kDa protein (dystrobrevin-2) that has a different C terminus, lacking the putative tyrosine kinase substrate domain. In skeletal and cardiac muscle, transcripts of 1.7 and 3.3/3.5 kilobases predominate and encode additional isoforms. Alternative splicing within the coding region and differential usage of untranslated regions produce additional variation. Multiple dystrobrevin-immunoreactive proteins copurify with syntrophin from mouse tissues. In skeletal muscle, dystrobrevin immunoreactivity is restricted to the neuromuscular junction and sarcolemma. The occurrence of many dystrobrevin isoforms is significant because alternative splicing and phosphorylation often have profound effects upon the biological activity of synaptic proteins.

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:	American Society for Biochemistry and Molecular Biology
ISSN:	0021-9258
Last Modified:	24 Oct 2022 11:50
URI:	https://orca.cardiff.ac.uk/id/eprint/49483

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