Luman is involved in osteoclastogenesis through the regulation of DC-STAMP expression, stability and localization

Soshi Kanemoto, Yasuhiro Kobayashi, Teruhito Yamashita, Takeshi Miyamoto, Min Cui, Rie Asada, Xiang Cui, Kenta Hino, Masayuki Kaneko, Tomoko Takai, Koji Matsuhisa, Naoyuki Takahashi, Kazunori Imaizumi

研究成果: Article査読

15 被引用数 (Scopus)

抄録

Luman (also known as CREB3) is a type-II transmembrane transcription factor belonging to the OASIS family that localizes to the endoplasmic reticulum (ER) membrane under normal conditions. In response to ER stress, OASIS-family members are subjected to regulated intramembrane proteolysis (RIP), following which the cleaved N-terminal fragments translocate to the nucleus. In this study, we show that treatment of bone marrow macrophages (BMMs) with cytokines - macrophage colony-stimulating factor (M-CSF) and RANKL (also known as TNFSF11) - causes a time-dependent increase in Luman expression, and that Luman undergoes RIP and becomes activated during osteoclast differentiation. Small hairpin (sh)RNA-mediated knockdown of Luman in BMMs prevented the formation of multinucleated osteoclasts, concomitant with the suppression of DC-STAMP, a protein that is essential for cell-cell fusion in osteoclastogenesis. The N-terminus of Luman facilitates promoter activity of DC-STAMP, resulting in upregulation of DC-STAMP expression. Furthermore, Luman interacts with DC-STAMP, and controls its stability and localization. These results suggest that Luman regulates the multinucleation of osteoclasts by promoting cell fusion of mononuclear osteoclasts through DC-STAMP induction and intracellular distribution during osteoclastogenesis.

本文言語English
ページ(範囲)4353-4365
ページ数13
ジャーナルJournal of Cell Science
128
23
DOI
出版ステータスPublished - 2015

ASJC Scopus subject areas

  • 細胞生物学

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