Kanagawa Motoi, Michele Daniel E, Satz Jakob S, Barresi Rita, Kusano Hajime, Sasaki Takako, Timpl Rupert, Henry Michael D, Campbell Kevin P
Department of Physiology and Biophysics, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, 400 Eckstein Medical Building, Iowa City, IA 52242, USA.
FEBS Lett. 2005 Aug 29;579(21):4792-6. doi: 10.1016/j.febslet.2005.07.059.
Dystroglycan is a cell-surface matrix receptor that requires LARGE-dependent glycosylation for laminin binding. Although the interaction of dystroglycan with laminin has been well characterized, less is known about the role of dystroglycan glycosylation in the binding and assembly of perlecan. We report reduced perlecan-binding activity and mislocalization of perlecan in the LARGE-deficient Large(myd) mouse. Cell-surface ligand clustering assays show that laminin polymerization promotes perlecan assembly. Solid-phase binding assays provide evidence for the first time of a trimolecular complex formation of dystroglycan, laminin and perlecan. These data suggest functional disruption of the trimolecular complex in glycosylation-deficient muscular dystrophy.
肌营养不良蛋白聚糖是一种细胞表面基质受体，它需要依赖LARGE的糖基化来结合层粘连蛋白。尽管肌营养不良蛋白聚糖与层粘连蛋白的相互作用已得到充分表征，但对于肌营养不良蛋白聚糖糖基化在基底膜聚糖的结合和组装中的作用了解较少。我们报道了在缺乏LARGE的Large（myd）小鼠中基底膜聚糖结合活性降低以及基底膜聚糖的定位错误。细胞表面配体聚集试验表明层粘连蛋白聚合促进基底膜聚糖组装。固相结合试验首次提供了肌营养不良蛋白聚糖、层粘连蛋白和基底膜聚糖形成三分子复合物的证据。这些数据表明糖基化缺陷型肌营养不良中三分子复合物的功能破坏。
