Myoneurin regulates BMP signaling by competing with Ppm1a for Smad binding

Shuyan Yang; Guozhu Ning; Yiming Hou; Yu Cao; Jin Xu; Jianxin Wu; Ting Zhang; Qiang Wang

doi:10.1016/j.isci.2022.104495

Myoneurin regulates BMP signaling by competing with Ppm1a for Smad binding

iScience. 2022 May 30;25(6):104495. doi: 10.1016/j.isci.2022.104495. eCollection 2022 Jun 17.

Authors

Shuyan Yang¹, Guozhu Ning^{2

3}, Yiming Hou³, Yu Cao³, Jin Xu², Jianxin Wu⁴, Ting Zhang¹, Qiang Wang^{2

3}

Affiliations

¹ Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China.
² Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, Guangzhou 510006, China.
³ State Key Laboratory of Membrane Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
⁴ Beijing TongRen Hospital, Capital Medical University, 17 Hougou Street, Chong Wen Men, Beijing 100005, PR China.

Abstract

A delicate balance of BMP activity is critical for tissue formation and organogenesis. However, the mechanical molecular details in ensuring the proper duration and intensity of BMP signaling have yet to be fully elucidated. Here, we identified a zebrafish mutant with a disrupted gene encoding for the BTB/POZ and zinc finger protein myoneurin (Mynn). mynn ^-/- mutants exhibited severe loss of pharyngeal cartilage elements, owing to poor proliferation, blocked differentiation, and low viability of cranial neural crest cells. Depletion of mynn in both zebrafish embryos and mammalian cells led to a reduction of the BMP signal activity. Mechanistically, Mynn interacts with Smad proteins in the nucleus, thereby disrupting the association between Smad protein and the phosphatase Ppm1a. Ultimately, this interaction prevents Smad dephosphorylation. More broadly, our findings may provide a new strategy to balance BMP signal activity via competitive binding of Mynn and Ppm1a to Smad proteins during pharyngeal cartilage formation.

Keywords: Cell biology; Developmental biology; Functional aspects of cell biology.