Pikachurin 与 dystroglycan 的相互作用因先天性肌营养不良模型中 O-甘露糖基化缺陷而减弱，通过 LARGE 过表达得到挽救。
Pikachurin interaction with dystroglycan is diminished by defective O-mannosyl glycosylation in congenital muscular dystrophy models and rescued by LARGE overexpression.
机构信息
Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY 13210, United States.
出版信息
Neurosci Lett. 2011 Feb 1;489(1):10-5. doi: 10.1016/j.neulet.2010.11.056. Epub 2010 Dec 1.
Abstract
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.
摘要
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。
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