Different dystrophin-like complexes are expressed in neurons and glia

Duchenne muscular dystrophy is a fatal muscle de disease that is often asso ciated with cognitive impairment. Accordingly, dystrophin is found at the m uscle sarcolemma and at postsynaptic sites in neurons. In muscle, dystrophi n forms part of a membrane-spanning complex. the dystrophin-associated prot ein complex (DPC). Whereas the composition of the DPC in muscle is well doc umented, the existence of a similar complex in brain remains largely unknow n. To determine the composition of DPC-like complexes in brain. we have exa mined the molecular associations and distribution of the dystrobrevins, a w idely 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-dystro brevin forms a specific complex with dystrophin and syntrophin, By contrast , alpha-dystrobrevin-1 is found in perivascular astrocytes and Bergmann gli a, and is not PSD-enriched, alpha-Dystrobrevin-1 is associated with Dp71, u trophin, and syntrophin. In the brains of mice that lack dystrophin and Dp7 1, the dystrobrevin-syntrophin complexes are still formed. whereas in dystr ophin-deficient muscle, the assembly of the DPC is disrupted. Thus, despite the similarity in primary sequence, alpha- and beta-dystrobrevin are diffe rentially distributed in the brain where they form separate DPC-like comple xes.