Defective glycosylation of α-dystroglycan contributes to podocyte flattening.
Defective glycosylation of α-dystroglycan contributes to podocyte flattening.
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DOI：
10.1038/ki.2010.403
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发表时间：
2011-02
影响因子：
19.6
通讯作者：
K. Kojima;Hitonari Nosaka;Y. Kishimoto;Yuri Nishiyama;S. Fukuda;Masaru Shimada;K. Kodaka;F. Saito;K. Matsumura;Teruo Shimizu;T. Toda;S. Takeda;H. Kawachi;S. Uchida
中科院分区：
文献类型：
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作者：
K. Kojima;Hitonari Nosaka;Y. Kishimoto;Yuri Nishiyama;S. Fukuda;Masaru Shimada;K. Kodaka;F. Saito;K. Matsumura;Teruo Shimizu;T. Toda;S. Takeda;H. Kawachi;S. Uchida
除了骨骼肌和神经系统外，足细胞基底膜中还发现了α-dystroglan，稳定了肾小球基底膜上的这些细胞。福汀是以导致福山型先天性肌营养不良症的基因命名的，是一种推测的糖基转移酶，需要对α-营养不良聚糖进行翻译后修饰。以两个等位基因为靶点的嵌合小鼠患有严重的肌营养不良症；然而，这些小鼠没有蛋白尿。尽管没有功能性肾功能缺陷，但我们评估了肾小球结构，并在光学显微镜下发现嵌合体小鼠有轻微异常。电子显微镜显示足细胞足突变平，与野生型小鼠相比，嵌合体中足细胞足突的数量明显减少。通过免疫印迹或免疫组织化学方法，抗层粘连蛋白结合糖基残基的单抗没有检测到α-营养不良聚糖在肾小球中的糖基化。相反，核心α-Dystroglan蛋白的表达被保留下来。免疫组织化学和实时荧光定量RT-PCR法显示，嵌合体小鼠的抗肌营养不良蛋白基因表达水平、neparin和α3-整合素蛋白的含量与野生型小鼠相比均无统计学差异。因此，我们的结果表明，适当的α-dystroglan的糖基化在维持足细胞的结构中起着重要的作用。
In addition to skeletal muscle and the nervous system, α-dystroglycan is found in the podocyte basal membrane, stabilizing these cells on the glomerular basement membrane. Fukutin, named after the gene responsible for Fukuyama-type congenital muscular dystrophy, is a putative glycosyltransferase required for the post-translational modification of α-dystroglycan. Chimeric mice targeted for both alleles offukutindevelop severe muscular dystrophy; however, these mice do not have proteinuria. Despite the lack of a functional renal defect, we evaluated glomerular structure and found minor abnormalities in the chimeric mice by light microscopy. Electron microscopy revealed flattening of podocyte foot processes, the number of which was significantly lower in the chimeric compared to wild-type mice. A monoclonal antibody against the laminin-binding carbohydrate residues of α-dystroglycan did not detect α-dystroglycan glycosylation in the glomeruli by immunoblotting or immunohistochemistry. In contrast, expression of the core α-dystroglycan protein was preserved. There was no statistical difference in dystroglycan mRNA expression or in the amount of nephrin and α3-integrin protein in the chimeric compared to the wild-type mice as judged by immunohistochemistry and real-time RT-PCR. Thus, our results indicate that appropriate glycosylation of α-dystroglycan has an important role in the maintenance of podocyte architecture.