Role of the ANKMY2-FKBP38 axis in regulation of the sonic hedgehog (Shh) signaling pathway

Shotaro Saita, Michiko Shirane, Tohru Ishitani, Nobuyuki Shimizu, Keiichi I. Nakayama

研究成果: Contribution to journalArticle査読

11 被引用数 (Scopus)

抄録

Sonic hedgehog (Shh) is a secreted morphogen that controls the patterning and growth of various tissues in the developing vertebrate embryo, including the central nervous system. Ablation of the FK506-binding protein 38 (FKBP38) gene results in activation of the Shh signaling pathway in mouse embryos, but the molecular mechanism by which FKBP38 suppresses Shh signaling has remained unclear. With the use of a proteomics approach, we have now identified ANKMY2, a protein with three ankyrin repeats and aMYND(myeloid, Nervy, and DEAF- 1)-type Zn2+finger domain, as a molecule that interacts with FKBP38. Co-immunoprecipitation analysis confirmed that endogenous FKBP38 andANKMY2interact in the mouse brain. Depletion or overexpression ofANKMY2resulted in down- and up-regulation of Shh signaling, respectively, in mouse embryonic fibroblasts. Furthermore, combined depletion of both FKBP38 and ANKMY2 attenuated Shh signaling in these cells, suggesting that ANKMY2 acts downstream of FKBP38 to activate the Shh signaling pathway. Targeting of the zebrafish ortholog of mouse Ankmy2 (ankmy2a) in fish embryos with an antisense morpholino oligonucleotide conferred a phenotype reflecting loss of function of the Shh pathway, suggesting that the regulation of Shh signaling by ANKMY2 is conserved between mammals and fish. Our findings thus indicate that the FKBP38-ANKMY2 axis plays a key role in regulation of Shh signaling in vivo.

本文言語英語
ページ(範囲)25639-25654
ページ数16
ジャーナルJournal of Biological Chemistry
289
37
DOI
出版ステータス出版済み - 9 12 2014

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 細胞生物学

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