期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/ijms22052455
关键词
neuromuscular junction; acetylcholine receptor; Wnt/beta-catenin signaling; FGF signaling
资金
- Japan Society for the Promotion of Science [JP17K07094, JP18K06483, JP19K22802, JP20K06925, JP20H03561]
- Ministry of Health, Labour, and Welfare of Japan [20FC1036]
- Japan Agency for Medical Research and Development [20gm1010002, JP20ek0109281, JP20ek0109488, 20bm0804005]
- National Center of Neurology and Psychiatry [2-5]
- Hori Sciences and Arts Foundation
This review focuses on secreted signaling molecules that regulate the clustering of acetylcholine receptors (AChRs) at the neuromuscular junction (NMJ), including neural agrin, Lrp4, MuSK, Rspo2, Fgf18, and Ctgf. These molecules play crucial roles in ensuring efficient signal transduction at the NMJ.
Signal transduction at the neuromuscular junction (NMJ) is affected in many human diseases, including congenital myasthenic syndromes (CMS), myasthenia gravis, Lambert-Eaton myasthenic syndrome, Isaacs' syndrome, Schwartz-Jampel syndrome, Fukuyama-type congenital muscular dystrophy, amyotrophic lateral sclerosis, and sarcopenia. The NMJ is a prototypic cholinergic synapse between the motor neuron and the skeletal muscle. Synaptogenesis of the NMJ has been extensively studied, which has also been extrapolated to further understand synapse formation in the central nervous system. Studies of genetically engineered mice have disclosed crucial roles of secreted molecules in the development and maintenance of the NMJ. In this review, we focus on the secreted signaling molecules which regulate the clustering of acetylcholine receptors (AChRs) at the NMJ. We first discuss the signaling pathway comprised of neural agrin and its receptors, low-density lipoprotein receptor-related protein 4 (Lrp4) and muscle-specific receptor tyrosine kinase (MuSK). This pathway drives the clustering of acetylcholine receptors (AChRs) to ensure efficient signal transduction at the NMJ. We also discuss three secreted molecules (Rspo2, Fgf18, and connective tissue growth factor (Ctgf)) that we recently identified in the Wnt/beta-catenin and fibroblast growth factors (FGF) signaling pathways. The three secreted molecules facilitate the clustering of AChRs by enhancing the agrin-Lrp4-MuSK signaling pathway.
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