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

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9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4353-4365
Number of pages13
JournalJournal of Cell Science
Volume128
Issue number23
DOIs
Publication statusPublished - Jan 1 2015

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All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Kanemoto, S., Kobayashi, Y., Yamashita, T., Miyamoto, T., Cui, M., Asada, R., ... Imaizumi, K. (2015). Luman is involved in osteoclastogenesis through the regulation of DC-STAMP expression, stability and localization. Journal of Cell Science, 128(23), 4353-4365. https://doi.org/10.1242/jcs.176057