Binding of PICK1 PDZ domain with calcineurin B regulates osteoclast differentiation

Yuya Kamano, Jun Watanabe, Tsutomu Iida, Takeru Kondo, Hiroko Okawa, Hirofumi Yatani, Makio Saeki, Hiroshi Egusa

研究成果: Article査読

1 被引用数 (Scopus)

抄録

The calcineurin/nuclear factor of activated T cell (NFAT) signaling pathway plays a major role in osteoclast differentiation; however, the proteins that react with the calcineurin-NFAT complex in osteoclasts to regulate osteoclastogenesis remain unclear. Here, we present evidence that PICK1 also positively regulates calcineurin B in osteoclasts to activate NFAT to promote osteoclastogenesis. mRNA and protein expression of PICK1 in murine primary bone marrow macrophages (BMMs) was significantly increased during RANKL-induced osteoclast differentiation. The interaction of PICK1 with calcineurin B in BMMs was confirmed by co-immunoprecipitation. An inhibitor of the PICK1 PDZ domain significantly decreased osteoclastogenesis marker gene expression and the number of TRAP-positive multinucleated cells among RAW264.7 osteoclast progenitor cells. Overexpression of PICK1 in RAW264.7 cells significantly increased the number of TRAP-positive mature osteoclasts. Increased NFAT activation with transcriptional activation of PICK1 during RAW264.7 osteoclastogenesis was also confirmed in a tetracycline-controlled PICK1 expression system. These results suggest that the PDZ domain of PICK1 directly interacts with calcineurin B in osteoclast progenitor cells and promotes osteoclast differentiation through activation of calcineurin-NFAT signaling.

本文言語English
ページ(範囲)83-88
ページ数6
ジャーナルBiochemical and biophysical research communications
496
1
DOI
出版ステータスPublished - 2018 1 29

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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