Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY 13210, United States.
Neurosci Lett. 2011 Feb 1;489(1):10-5. doi: 10.1016/j.neulet.2010.11.056. Epub 2010 Dec 1.
Congenital muscular dystrophies (CMD) such as muscle-eye-brain disease caused by defective glycosylation of α-dystroglycan (α-DG) exhibit defective photoreceptor synaptic function. Mouse knockouts of dystroglycan and its extracellular matrix binding partner pikachurin recapitulate this phenotype. In this study, pikachurin-α-dystroglycan interactions in several mouse models of CMD were examined by pikachurin overlay experiments. The results show that hypoglycosylation of α-dystroglycan resulted in markedly reduced pikachurin-α-dystroglycan interactions. Expression of pikachurin is abolished at the outer plexiform layer of two mouse models, protein O-mannose N-acetylglucosaminyl transferase 1 (POMGnT1) knockout and Large(myd) mice. Overexpressing LARGE restored this interaction in POMGnT1 knockout cells. These results indicate that pikachurin interactions with α-dystroglycan and its localization at the photoreceptor ribbon synapse require normal glycosylation of α-dystroglycan.
先天性肌肉营养不良症（CMD），如由于α- 肌营养不良聚糖（α-DG）糖基化缺陷引起的肌肉眼脑疾病，表现出感光器突触功能缺陷。通过敲除肌营养不良蛋白和其细胞外基质结合伴侣 pikachurin 的小鼠模型可重现这一表型。在这项研究中，通过 pikachurin 覆盖实验检查了几种 CMD 小鼠模型中的 pikachurin-α- 肌营养不良聚糖相互作用。结果表明，α- 肌营养不良聚糖的低聚糖化导致 pikachurin-α- 肌营养不良聚糖相互作用明显减少。两种小鼠模型（POMGnT1 敲除和 Large(myd) 小鼠）的外丛状层中 pikachurin 的表达被消除。过表达 LARGE 可恢复 POMGnT1 敲除细胞中的这种相互作用。这些结果表明，pikachurin 与α- 肌营养不良聚糖的相互作用及其在光感受器带状突触的定位需要α- 肌营养不良聚糖的正常糖基化。
