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Atp6v0d2 Is an Essential Component of the Osteoclast-Specific Proton Pump That Mediates Extracellular Acidification in Bone Resorption

文献类型:期刊论文

作者Wu, HP; Xu, GL; Li, YP
刊名JOURNAL OF BONE AND MINERAL RESEARCH
出版日期2009
卷号24期号:5页码:871-885
关键词Atp6v0d2 vacuolar-ATPases osteoclasts bone resorption extracellular acidification
通讯作者Li, YP (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA.,ypli@forsyth.org
英文摘要Bone resorption relies on the extracellular acidification function of vacuolar (V-) ATPase proton pump(s) present in the plasma membrane of osteoclasts. The exact configuration of osteoclast-specific V-ATPases remains largely unknown. In this study, we found that Atp6v0d2 (d2), an isoform of the d subunit in the V-ATPase, showed 5-fold higher expression than that of Atp6v0d1. (d1) in mature osteoclasts, indicating a potential function in osteoclastic bone resorption. When d2 was depleted at an earl), stage of RANKL-induced osteoclast differentiation in vitro, formation of multinucleated cells was severely impaired. However, depletion of d2 at a late differentiation stage did not affect osteoclast fusion but did abolish the activity of extracellular acidification and bone resorption of mature osteoclasts. We also showed the association of the two tagged-proteins d2 and a3 when co-expressed in mammalian cells with a co-immunoprecipitation assay. Moreover, glutathione-S-transferase (GST) pull-down assay showed the direct interaction of d2 with the N terminus of Atp6v0a3 (0), which is the functionally identified osteoclast-specific component of V-ATPase. Therefore, our results show the dual function of d2 as a regulator of cell fusion in osteoclast differentiation and as an essential component of the osteoclast-specific proton pump that mediates extracellular acidification in bone resorption.
学科主题Endocrinology & Metabolism
类目[WOS]Endocrinology & Metabolism
关键词[WOS]VACUOLAR H+-ATPASE ; V-ATPASE ; TRANSLOCATING ATPASE ; D-SUBUNIT ; C-SUBUNIT ; STIMULATING FACTOR ; MOLECULAR-CLONING ; GENE-EXPRESSION ; A3 ISOFORM ; DIFFERENTIATION
收录类别SCI
语种英语
WOS记录号WOS:000265550000014
版本出版稿
源URL[http://202.127.25.143/handle/331003/1194]  
专题上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式
GB/T 7714
Wu, HP,Xu, GL,Li, YP. Atp6v0d2 Is an Essential Component of the Osteoclast-Specific Proton Pump That Mediates Extracellular Acidification in Bone Resorption[J]. JOURNAL OF BONE AND MINERAL RESEARCH,2009,24(5):871-885.
APA Wu, HP,Xu, GL,&Li, YP.(2009).Atp6v0d2 Is an Essential Component of the Osteoclast-Specific Proton Pump That Mediates Extracellular Acidification in Bone Resorption.JOURNAL OF BONE AND MINERAL RESEARCH,24(5),871-885.
MLA Wu, HP,et al."Atp6v0d2 Is an Essential Component of the Osteoclast-Specific Proton Pump That Mediates Extracellular Acidification in Bone Resorption".JOURNAL OF BONE AND MINERAL RESEARCH 24.5(2009):871-885.

入库方式: OAI收割

来源:上海生物化学与细胞生物学研究所

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