Luman, an ER membrane-bound transcription factor, is involved in osteoclastogenesis

2014 Fiscal Year Final Research Report

• Project/Area Number: 25861324
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Hiroshima University
• Principal Investigator: KANEMOTO Soshi 広島大学, 医歯薬保健学研究院, 助教 (90611913)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 破骨細胞 / 小胞体 / 転写因子 / 分化 / 細胞融合

Outline of Final Research Achievements

Luman 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 processed, and cleaved N-terminal fragments translocate to the nucleus and function as a transcription factor. In this study, it was revealed that Luman is induced and activated during osteoclast differentiation. ShRNA-mediated knockdown of Luman prevents the formation of multinucleated osteoclasts, concomitant with the suppression of DC-STAMP, a protein essential for cell-cell fusion in osteoclastogenesis. N-terminus of Luman leads to up-regulation of DC-STAMP expression. Moreover, 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.

Free Research Field

生化学