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- Title
Muscle Yap Is a Regulator of Neuromuscular Junction Formation and Regeneration.
- Authors
Kai Zhao; Chengyong Shen; Yisheng Lu; Zhihui Huang; Lei Li; Rand, Christopher D.; Jinxiu Pan; Xiang-Dong Sun; Zhibing Tan; Hongsheng Wang; Guanglin Xing; Yu Cao; Guoqing Hu; Jiliang Zhou; Wen-Cheng Xiong; Lin Mei
- 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.
- Subjects
PROTEINS; CELL proliferation; CELL differentiation; SYNAPSES; MUSCLES
- Publication
Journal of Neuroscience, 2017, Vol 37, Issue 13, p3465
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2934-16.2017