Muscle yap is a regulator of neuromuscular junction formation and regeneration

Kai Zhao, Chengyong Shen, Yisheng Lu, Zhihui Huang, Lei Li, Christopher D. Rand, Jinxiu Pan, Xiang Dong Sun, Zhibing Tan, Hongsheng Wang, Guanglin Xing, Yu Cao, Guoqing Hu, Jiliang Zhou, Wen Cheng Iong, Lin Mei

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Yes-associated protein (Yap) is a major effector of the Hippo pathway that regulates cell proliferation and differentiation during development and restricts tissue growth in adult animals. However, its role in synapse formation remains poorly understood. In this study, we characterized Yap’s role in the formation of the neuromuscular junction (NMJ). In HSA-Yap-/- mice where Yap was mutated specifically in muscle cells, AChR clusters were smaller and were distributed in a broader region in the middle of muscle fibers, suggesting that muscle Yap is necessary for the size and location of AChR clusters. In addition, HSA-Yap-/- mice also exhibited remarkable presynaptic deficits. Many AChR clusters were not or less covered by nerve terminals; miniature endplate potential frequency was reduced, which was associated with an increase in paired-pulse facilitation, indicating structural and functional defects. In addition, muscle Yap mutation prevented reinnervation of denervated muscle fibers. Together, these observations indicate a role of muscle Yap in NMJ formation and regeneration. We found that β-catenin was reduced in the cytoplasm and nucleus of mutant muscles, suggesting compromised β-catenin signaling. Both NMJ formation and regeneration deficits of HSA-Yap-/- mice were ameliorated by inhibiting β-catenin degradation, further corroborating a role of β-catenin or Wnt-dependent signaling downstream of Yap to regulate NMJ formation and regeneration.

Original languageEnglish (US)
Pages (from-to)3465-3477
Number of pages13
JournalJournal of Neuroscience
Volume37
Issue number13
DOIs
StatePublished - Mar 29 2017

Keywords

  • Neuromuscular junction
  • Regeneration
  • YAP
  • β-catenin

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Zhao, K., Shen, C., Lu, Y., Huang, Z., Li, L., Rand, C. D., Pan, J., Sun, X. D., Tan, Z., Wang, H., Xing, G., Cao, Y., Hu, G., Zhou, J., Iong, W. C., & Mei, L. (2017). Muscle yap is a regulator of neuromuscular junction formation and regeneration. Journal of Neuroscience, 37(13), 3465-3477. https://doi.org/10.1523/JNEUROSCI.2934-16.2017