Department of Genetics, Cell Biology, and Development, Developmental Biology Center, University of Minnesota, Minneapolis, MN 55455, USA.
J Cell Biol. 2011 Jan 24;192(2):349-63. doi: 10.1083/jcb.201006109. Epub 2011 Jan 17.
The dystrophin protein complex (DPC), composed of dystrophin and associated proteins, is essential for maintaining muscle membrane integrity. The link between mutations in dystrophin and the devastating muscle failure of Duchenne's muscular dystrophy (DMD) has been well established. Less well appreciated are the accompanying cognitive impairment and neuropsychiatric disorders also presented in many DMD patients, which suggest a wider role for dystrophin in membrane-cytoskeleton function. This study provides genetic evidence of a novel role for DYS-1/dystrophin in maintaining neural organization in Caenorhabditis elegans. This neuronal function is distinct from the established role of DYS-1/dystrophin in maintaining muscle integrity and regulating locomotion. SAX-7, an L1 cell adhesion molecule (CAM) homologue, and STN-2/γ-syntrophin also function to maintain neural integrity in C. elegans. This study provides biochemical data that show that SAX-7 associates with DYS-1 in an STN-2/γ-syntrophin-dependent manner. These results reveal a recruitment of L1CAMs to the DPC to ensure neural integrity is maintained.
肌营养不良蛋白复合物（DPC）由肌营养不良蛋白和相关蛋白组成，对于维持肌肉膜的完整性至关重要。肌营养不良蛋白突变与杜氏肌营养不良症（DMD）毁灭性的肌肉衰竭之间的联系已得到充分证实。然而，人们对 DMD 患者中也存在的伴随认知障碍和神经精神障碍认识不足，这表明肌营养不良蛋白在膜-细胞骨架功能中具有更广泛的作用。这项研究为 DYS-1/肌营养不良蛋白在维持秀丽隐杆线虫神经组织中的新作用提供了遗传证据。这种神经元功能与 DYS-1/肌营养不良蛋白在维持肌肉完整性和调节运动的既定作用不同。SAX-7，一种 L1 细胞黏附分子（CAM）同源物，以及 STN-2/γ- 连接素也在秀丽隐杆线虫中发挥作用，以维持神经完整性。这项研究提供了生化数据，表明 SAX-7 以 STN-2/γ- 连接素依赖的方式与 DYS-1 结合。这些结果揭示了 L1CAM 被招募到 DPC 以确保神经完整性得以维持。
