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

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), foll...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712816/
https://www.ncbi.nlm.nih.gov/pubmed/26503158
http://dx.doi.org/10.1242/jcs.176057
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author 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
author_facet 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
author_sort Kanemoto, Soshi
collection PubMed
description 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.
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spelling pubmed-47128162016-02-05 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 J Cell Sci Research Article 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. The Company of Biologists 2015-12-01 /pmc/articles/PMC4712816/ /pubmed/26503158 http://dx.doi.org/10.1242/jcs.176057 Text en © 2015. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
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
Luman is involved in osteoclastogenesis through the regulation of DC-STAMP expression, stability and localization
title Luman is involved in osteoclastogenesis through the regulation of DC-STAMP expression, stability and localization
title_full Luman is involved in osteoclastogenesis through the regulation of DC-STAMP expression, stability and localization
title_fullStr Luman is involved in osteoclastogenesis through the regulation of DC-STAMP expression, stability and localization
title_full_unstemmed Luman is involved in osteoclastogenesis through the regulation of DC-STAMP expression, stability and localization
title_short Luman is involved in osteoclastogenesis through the regulation of DC-STAMP expression, stability and localization
title_sort luman is involved in osteoclastogenesis through the regulation of dc-stamp expression, stability and localization
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712816/
https://www.ncbi.nlm.nih.gov/pubmed/26503158
http://dx.doi.org/10.1242/jcs.176057
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