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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.

Copyright (C) 1999, The Rockefeller University Press