1. Academic Validation
  2. Dual function of VGLL4 in muscle regeneration

Dual function of VGLL4 in muscle regeneration

  • EMBO J. 2019 Sep 2;38(17):e101051. doi: 10.15252/embj.2018101051.
Xue Feng 1 Zuoyun Wang 1 Fei Wang 1 Tiantian Lu 1 Jinjin Xu 1 Xueyan Ma 1 Jinhui Li 1 Lingli He 1 Wenxiang Zhang 1 Sheng Li 1 Wenjun Yang 1 Shu Zhang 1 Gaoxiang Ge 1 Yun Zhao 1 2 Ping Hu 1 3 Lei Zhang 1 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • 2 School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • 3 Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.
Abstract

VGLL4 has previously been identified as a negative regulator of YAP. Here we show that VGLL4 regulates muscle regeneration in both YAP-dependent and YAP-independent manners at different stages. Knockout of VGLL4 in mice leads to smaller myofiber size and defective muscle contraction force. Furthermore, our studies reveal that knockout of VGLL4 results in increased muscle satellite cells proliferation and impaired myoblast differentiation, which ultimately leads to delayed muscle regeneration. Mechanistically, the results show that VGLL4 works as a conventional repressor of YAP at the proliferation stage of muscle regeneration. At the differentiation stage, VGLL4 acts as a co-activator of TEAD4 to promote MyoG transactivation and facilitate the initiation of differentiation in a YAP-independent manner. Moreover, VGLL4 stabilizes the protein-protein interactions between MyoD and TEAD4 to achieve efficient MyoG transactivation. Our findings define the dual roles of VGLL4 in regulating muscle regeneration at different stages and may open novel therapeutic perspectives for muscle regeneration.

Keywords

MyoD; MyoG; TEAD4; VGLL4; muscle regeneration.

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