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 language | English |
|---|---|
| Pages (from-to) | 4353-4365 |
| Number of pages | 13 |
| Journal | Journal of Cell Science |
| Volume | 128 |
| Issue number | 23 |
| DOIs | |
| Publication status | Published - Jan 1 2015 |
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All Science Journal Classification (ASJC) codes
- Cell Biology
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Luman is involved in osteoclastogenesis through the regulation of DC-STAMP expression, stability and localization. / Kanemoto, Soshi; Kobayashi, Yasuhiro; Yamashita, Teruhito; Miyamoto, Takeshi; Cui, Min; Asada, Rie; Cui, Xiang; Hino, Kenta; Kaneko, Masayuki; Takai, Tomoko; Matsuhisa, Koji; Takahashi, Naoyuki; Imaizumi, Kazunori.
In: Journal of Cell Science, Vol. 128, No. 23, 01.01.2015, p. 4353-4365.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Luman is involved in osteoclastogenesis through the regulation of DC-STAMP expression, stability and localization
AU - Kanemoto, Soshi
AU - Kobayashi, Yasuhiro
AU - Yamashita, Teruhito
AU - Miyamoto, Takeshi
AU - Cui, Min
AU - Asada, Rie
AU - Cui, Xiang
AU - Hino, Kenta
AU - Kaneko, Masayuki
AU - Takai, Tomoko
AU - Matsuhisa, Koji
AU - Takahashi, Naoyuki
AU - Imaizumi, Kazunori
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84949920854&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84949920854&partnerID=8YFLogxK
U2 - 10.1242/jcs.176057
DO - 10.1242/jcs.176057
M3 - Article
C2 - 26503158
AN - SCOPUS:84949920854
VL - 128
SP - 4353
EP - 4365
JO - Journal of Cell Science
JF - Journal of Cell Science
SN - 0021-9533
IS - 23
ER -