Tian M, Jacobson C, Gee S H, Campbell K P, Carbonetto S, Jucker M
Gerontology Research Center, National Institute on Aging, National Institute of Health, Baltimore, MD 21224, USA.
Eur J Neurosci. 1996 Dec;8(12):2739-47. doi: 10.1111/j.1460-9568.1996.tb01568.x.
Dystroglycan is a core component of the dystrophin receptor complex in skeletal muscle which links the extracellular matrix to the muscle cytoskeleton. Dystrophin, dystrophin-related protein (DRP, utrophin) and dystroglycan are present not only in muscles but also in the brain. Dystrophin is expressed in certain neuronal populations while DRP is associated with perivascular astrocytes. To gain insights into the function and molecular interactions of dystroglycan in the brain, we examined the localization of alpha- and beta-dystroglycan at the cellular and subcellular levels in the rat cerebellum. In blood vessels, we find alpha-dystroglycan associated with the laminin alpha 2-chain-rich parenchymal vascular basement membrane and beta-dystroglycan associated with the endfeet of perivascular astrocytes. We also show that alpha-dystroglycan purified from the brain binds alpha 2-chain-containing laminin-2. These observations suggest a dystroglycan-mediated linkage between DRP in perivascular astrocytic endfeet and laminin-2 in the parenchymal basement membrane similar to that described in skeletal muscle. This linkage of the astrocytic endfeet to the vascular basement membrane is likely to be important for blood vessel formation and stabilization and for maintaining the integrity of the blood-brain barrier. In addition to blood vessel labelling, we show that alpha-dystroglycan in the rat cerebellum is associated with the surface of Purkinje cell bodies, dendrites and dendritic spines. Dystrophin has previously been localized to the inner surface of the plasma membrane of Purkinje cells and is enriched at postsynaptic sites. Thus, the present results also support the hypothesis that dystrophin interacts with dystroglycan in cerebellar Purkinje neurons.
肌营养不良聚糖是骨骼肌中肌营养不良蛋白受体复合物的核心成分，它将细胞外基质与肌肉细胞骨架连接起来。肌营养不良蛋白、肌营养不良相关蛋白（DRP，抗肌萎缩蛋白）和肌营养不良聚糖不仅存在于肌肉中，也存在于大脑中。肌营养不良蛋白在某些神经元群体中表达，而DRP与血管周围星形胶质细胞相关。为了深入了解肌营养不良聚糖在大脑中的功能和分子相互作用，我们在大鼠小脑中研究了α - 和β - 肌营养不良聚糖在细胞和亚细胞水平的定位。在血管中，我们发现α - 肌营养不良聚糖与富含层粘连蛋白α2链的实质血管基底膜相关，β - 肌营养不良聚糖与血管周围星形胶质细胞的终足相关。我们还表明，从大脑中纯化的α - 肌营养不良聚糖与含α2链的层粘连蛋白 - 2结合。这些观察结果表明，血管周围星形胶质细胞终足中的DRP与实质基底膜中的层粘连蛋白 - 2之间存在肌营养不良聚糖介导的联系，类似于在骨骼肌中所描述的那样。星形胶质细胞终足与血管基底膜的这种联系可能对血管形成和稳定以及维持血脑屏障的完整性很重要。除了血管标记外，我们还表明大鼠小脑中的α - 肌营养不良聚糖与浦肯野细胞体、树突和树突棘的表面相关。肌营养不良蛋白先前已定位在浦肯野细胞质膜的内表面，并在突触后位点富集。因此，目前的结果也支持肌营养不良蛋白在小脑浦肯野神经元中与肌营养不良聚糖相互作用的假说。
