Luman is involved in osteoclastogenesis through the regulation of DC-STAMP expression, stability and localization.
J Cell Sci
; 128(23): 4353-65, 2015 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-26503158
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.
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Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Osteoclastos
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Células da Medula Óssea
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Diferenciação Celular
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Regulação da Expressão Gênica
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Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico
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Macrófagos
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Proteínas de Membrana
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Proteínas do Tecido Nervoso
Limite:
Animals
Idioma:
En
Revista:
J Cell Sci
Ano de publicação:
2015
Tipo de documento:
Article