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. 2021 Feb 28;22(5):2455. doi: 10.3390/ijms22052455

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Schematic of the neuromuscular junction and representative signaling molecules involved in nicotinic acetylcholine receptor (AChR) clustering by muscle-specific receptor tyrosine kinase (MuSK) phosphorylation, and/or by gene expression. Agrin binds to lipoprotein receptor-related protein 4 (Lrp4) to phosphorylate MuSK (Section 3). Connective tissue growth factor (Ctgf) also binds to Lrp4 to enhance MuSK phosphorylation (Section 3). Wnt modulates MuSK phosphorylation by associating with either Frizzled (not shown) or Lrp4, or both (Section 5). Rspo2 binds to Lgr5 to enhance MuSK phosphorylation (Section 5). Fibroblast growth factor 18 (Fgf18) binds to Fgfrs (Section 6), and neuregulin-1 (Nrg1) binds to ErbBs (Section 7), to enhance MuSK phosphorylation and induce expression of neuromuscular junction (NMJ)-specific genes.