Different dystrophin-like complexes are expressed in neurons and glia.
Duchenne muscular dystrophy is a fatal muscle disease that is often associated with cognitive impairment. Accordingly, dystrophin is found at the muscle sarcolemma and at postsynaptic sites in neurons. In muscle, dystrophin forms part of a membrane-spanning complex, the dystrophin-associated protein complex (DPC). Whereas the composition of the DPC in muscle is well documented, the existence of a similar complex in brain remains largely unknown. To determine the composition of DPC-like complexes in brain, we have examined the molecular associations and distribution of the dystrobrevins, a widely expressed family of dystrophin-associated proteins, some of which are components of the muscle DPC. beta-Dystrobrevin is found in neurons and is highly enriched in postsynaptic densities (PSDs). Furthermore, beta-dystrobrevin forms a specific complex with dystrophin and syntrophin. By contrast, alpha-dystrobrevin-1 is found in perivascular astrocytes and Bergmann glia, and is not PSD-enriched. alpha-Dystrobrevin-1 is associated with Dp71, utrophin, and syntrophin. In the brains of mice that lack dystrophin and Dp71, the dystrobrevin-syntrophin complexes are still formed, whereas in dystrophin-deficient muscle, the assembly of the DPC is disrupted. Thus, despite the similarity in primary sequence, alpha- and beta-dystrobrevin are differentially distributed in the brain where they form separate DPC-like complexes.
Blake
D J
DJ
Department of Human Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, United Kingdom. dblake@enterprise.molbiol.ox.ac.uk
Hawkes
R
R
Benson
M A
MA
Beesley
P W
PW
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D016189:Dystrophin / Q000031:analogs & derivatives / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D049029:Dystrophin-Associated Proteins; D017353:Gene Deletion; D007106:Immune Sera / Q000276:immunology; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051381:Rats; D012995:Solubility; D013574:Synaptosomes / Q000378:metabolism; D049411:Utrophin
D003598:Cytoskeletal Proteins; D016189:Dystrophin; D049029:Dystrophin-Associated Proteins; D007106:Immune Sera; D008565:Membrane Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C483600:Utrn protein, mouse; D049411:Utrophin; C085339:apo-dystrophin 1; C098885:dystrobrevin; C033652:postsynaptic density proteins; C091824:syntrophin