Isoform Diversity of Dystrobrevin, the Murine 87-kDa Postsynaptic Protein

doi:10.1074/jbc.271.13.7802

Isoform Diversity of Dystrobrevin, the Murine 87-kDa Postsynaptic Protein (*)

From the Molecular Genetics Group, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom and the
Department of Physiology, University of North Carolina, Chapel Hill, North Carolina 27599-7545

^§§To whom correspondence should be addressed.
Genetics Lab., Dept. of Biochemistry, University of Oxford, South Parks Rd., Oxford OX1 3QU, UK.
Tel.: 44-1865-275317; Fax: 44-1865-275215.

↵^¶ Present address: Genetics Lab., Dept. of Biochemistry, University of Oxford, South Parks Rd., Oxford OX1 3QU, United Kingdom.

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.

Footnotes

↵^§ Contributed equally to this work.
↵** Supported by an Ausbildungsstipendium from the Deutsche Forschungsgemeinshaft.
↵* This work was supported in part by grants from the Muscular Dystrophy Group of Great Britain and Northern Ireland, the Muscular Dystrophy Association of the United States of America (to K. E. D. and S. C. F.), the Medical Research Council, and the National Institutes of Health (to S. C. F.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank(™)/EMBL Data Bank with accession number(s) X95226 and X95227.
↵¹ The abbreviations used are:

NMJ

neuromuscular junction

AChR

acetylcholine receptor

DGC

dystrophin-associated glycoprotein complex

mAb

monoclonal antibody

Ab

anti-peptide antibody

kb

kilobase(s)

RT-PCR

reverse transcriptase-polymerase chain reaction

UTR

untranslated region

vr

variable region.
↵²D. J. Blake and K. E. Davies, unpublished data.
- Received June 29, 1995.
- Revision received January 5, 1996.