Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing, 210096, China.
The Southern Modern Forestry Collaborative Innovation Center, State Key Laboratory of Tree Genetics and Breeding, Nanjing Forestry University, Nanjing, 210037, China.
Commun Biol. 2024 Nov 9;7(1):1481. doi: 10.1038/s42003-024-07191-5.
Neurexin, a molecule associated with autism spectrum disorders, is thought to function mainly in neurons. Recently, it was reported that Neurexin is also present in muscle, but the role of Neurexin in muscle is still poorly understood. Here, we demonstrate that the overexpression of Neurexin in muscles effectively restored the locomotor function of Drosophila neurexin mutants, while rescuing effects are observed within the nervous. Notably, the defects in muscle structure and function caused by Neurexin deficiency were similar to those caused by mutations in dystroglycan, a gene associated with progressive muscular dystrophy. The absence of Neurexin leads to muscle attachment defects, emphasizing the essential role of Neurexin in muscle integrity. Furthermore, Neurexin deficiency reduces Dystroglycan glycosylation on the cell surface, which is crucial for maintaining proper muscle structure and function. Finally, Neurexin guides Dystroglycan to the glycosyltransferase complex through interactions with Rotated Abdomen, a homolog of mammalian POMT1. Our findings reveal that Neurexin mediates muscle development and function through Dystroglycan glycosylation, suggesting a potential association between autism spectrum disorders and muscular dystrophy.
神经连接蛋白是一种与自闭症谱系障碍相关的分子，被认为主要在神经元中发挥作用。最近有报道称，神经连接蛋白也存在于肌肉中，但神经连接蛋白在肌肉中的作用仍知之甚少。在这里，我们证明了在肌肉中过度表达神经连接蛋白可以有效地恢复果蝇神经连接蛋白突变体的运动功能，而这种拯救作用发生在神经系统内。值得注意的是，神经连接蛋白缺乏引起的肌肉结构和功能缺陷与肌营养不良症相关基因 dystroglycan 的突变引起的缺陷相似。神经连接蛋白的缺失导致肌肉附着缺陷，强调了神经连接蛋白在肌肉完整性中的重要作用。此外，神经连接蛋白缺乏会减少细胞表面上 Dystroglycan 的糖基化，这对于维持肌肉的正常结构和功能至关重要。最后，神经连接蛋白通过与 Rotated Abdomen（哺乳动物 POMT1 的同源物）的相互作用将 Dystroglycan 引导至糖基转移酶复合物。我们的研究结果表明，神经连接蛋白通过 Dystroglycan 的糖基化来介导肌肉的发育和功能，这提示了自闭症谱系障碍和肌肉营养不良症之间可能存在关联。
