Moukhles H, Carbonetto S
Centre for Research in Neuroscience, McGill University and Montreal General Hospital Research Institute, Montreal, Quebec, Canada.
J Neurochem. 2001 Aug;78(4):824-34. doi: 10.1046/j.1471-4159.2001.00466.x.
In muscle, dystrophin anchors a complex of proteins at the cell surface which includes alpha-dystroglycan, beta-dystroglycan, syntrophins and dystrobrevins. Mutations in the dystrophin gene lead to muscular dystrophy and mental retardation. In contrast to muscle, little is known about the localization and the molecular interactions of dystrophin and dystrophin associated proteins (DAPs) in brain. In the present study, we show that alpha-dystroglycan and dystrophin are localized to large neurones in cerebral cortex, hippocampus, cerebellum and spinal cord. Furthermore, we show that dystroglycan is a member of three distinct dystrophin-containing complexes. Two of these complexes contain syntrophin and both dystrophin and syntrophin are enriched in post-synaptic densities. These data suggest that dystrophin and DAPs may have a role in the organization of CNS synapses. Interestingly, the enrichment for syntrophin in post-synaptic densities is not affected in mice mutant for all dystrophin isoforms. Thus in the brain, unlike in muscle, the association of syntrophin with dystrophin is not crucial for the DAP complex which suggests that it may be associated with other proteins.
在肌肉中，肌营养不良蛋白将一组蛋白质复合物锚定在细胞表面，该复合物包括α - 肌营养不良聚糖、β - 肌营养不良聚糖、肌营养不良蛋白结合蛋白和短肌营养不良蛋白。肌营养不良蛋白基因的突变会导致肌肉萎缩症和智力发育迟缓。与肌肉不同，关于肌营养不良蛋白及其相关蛋白（DAPs）在大脑中的定位和分子相互作用知之甚少。在本研究中，我们发现α - 肌营养不良聚糖和肌营养不良蛋白定位于大脑皮层、海马体、小脑和脊髓中的大型神经元。此外，我们发现肌营养不良聚糖是三种不同的含肌营养不良蛋白复合物的成员。其中两种复合物含有肌营养不良蛋白结合蛋白，并且肌营养不良蛋白和肌营养不良蛋白结合蛋白在突触后致密物中富集。这些数据表明，肌营养不良蛋白和DAPs可能在中枢神经系统突触的组织中发挥作用。有趣的是，在所有肌营养不良蛋白异构体的突变小鼠中，突触后致密物中肌营养不良蛋白结合蛋白的富集不受影响。因此，在大脑中，与肌肉不同，肌营养不良蛋白结合蛋白与肌营养不良蛋白的结合对于DAP复合物并不关键，这表明它可能与其他蛋白质相关。
