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Rab44, a novel large Rab GTPase, negatively regulates osteoclast differentiation by modulating intracellular calcium levels followed by NFATc1 activation


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タイトル: Rab44, a novel large Rab GTPase, negatively regulates osteoclast differentiation by modulating intracellular calcium levels followed by NFATc1 activation
その他のタイトル: 新規高分子Rabタンパク質Rab44はNFATc1活性化を起こす細胞内カルシウムレベルを変動させることによって破骨細胞分化を負に制御する
著者: 山口, 優
著者(別表記) : Yamaguchi, Yu
発行日: 2017年12月 6日
出版者: Springer International Publishing
引用: Nagasaki University (長崎大学), 博士(歯学) (2017-12-06)
抄録: Rab44 is an atypical Rab GTPase that contains some additional domains such as the EF-hand and coiled-coil domains as well as Rab-GTPase domain. Although Rab44 genes have been found in mammalian genomes, no studies concerning Rab44 have been reported yet. Here, we identified Rab44 as an upregulated protein during osteoclast differentiation. Knockdown of Rab44 by small interfering RNA promotes RANKL-induced osteoclast differentiation of the murine monocytic cell line, RAW-D or of bone marrow-derived macrophages (BMMs). In contrast, overexpression of Rab44 prevents osteoclast differentiation. Rab44 was localized in the Golgi complex and lysosomes, and Rab44 overexpression caused an enlargement of early endosomes. A series of deletion mutant studies of Rab44 showed that the coiled-coil domain and lipidation sites of Rab44 is important for regulation of osteoclast differentiation. Mechanistically, Rab44 affects nuclear factor of activated T-cells c1 (NFATc1) signaling in RANKL-stimulated macrophages. Moreover, Rab44 depletion caused an elevation in intracellular Ca2+ transients upon RANKL stimulation, and particularly regulated lysosomal Ca2+ influx. Taken together, these results suggest that Rab44 negatively regulates osteoclast differentiation by modulating intracellular Ca2+ levels followed by NFATc1 activation.
記述: 長崎大学学位論文 学位記番号:博(医歯薬)甲第1003号 学位授与年月日:平成29年12月6日 / Author: Yu Yamaguchi, Eiko Sakai, Kuniaki Okamoto, Hiroshi Kajiya, Koji Okabe, Mariko Naito, Tomoko Kadowaki, Takayuki Tsukuba / Citation: Cellular and Molecular Life Sciences, 75(1), pp.33-48; 2018
キーワード: Rab44 / Rab GTPase / Osteoclast / Intracellular Ca2+ levels / NFATc1
URI: http://hdl.handle.net/10069/37983
ISSN: 1420682X
DOI: 10.1007/s00018-017-2607-9
関連リンク : http://hdl.handle.net/10069/37913
権利: © Springer International Publishing AG 2017 / The final publication is available at link.springer.com
資料タイプ: Thesis or Dissertation
原稿種類: ETD
出現コレクション:110 学位論文

引用URI : http://hdl.handle.net/10069/37983

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