論文

査読有り
2017年3月

Actin-binding protein coronin 1A controls osteoclastic bone resorption by regulating lysosomal secretion of cathepsin K

SCIENTIFIC REPORTS
  • Saori Ohmae
  • ,
  • Naruto Noma
  • ,
  • Masayasu Toyomoto
  • ,
  • Masahiro Shinohara
  • ,
  • Masatoshi Takeiri
  • ,
  • Hiroaki Fuji
  • ,
  • Kenji Takemoto
  • ,
  • Keiko Iwaisako
  • ,
  • Tomoko Fujita
  • ,
  • Norihiko Takeda
  • ,
  • Makoto Kawatani
  • ,
  • Mineyoshi Aoyama
  • ,
  • Masatoshi Hagiwara
  • ,
  • Yasushi Ishihama
  • ,
  • Masataka Asagiri

7
開始ページ
1
終了ページ
12
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/srep41710
出版者・発行元
NATURE PUBLISHING GROUP

Osteoclasts degrade bone matrix proteins via the secretion of lysosomal enzymes. However, the precise mechanisms by which lysosomal components are transported and fused to the bone-apposed plasma membrane, termed ruffled border membrane, remain elusive. Here, we identified coronin 1A as a negative regulator of exocytotic release of cathepsin K, one of the most important bone-degrading enzymes in osteoclasts. The modulation of coronin 1A expression did not alter osteoclast differentiation and extracellular acidification, but strongly affected the secretion of cathepsin K and osteoclast bone-resorption activity, suggesting the coronin 1A-mediated regulation of lysosomal trafficking and protease exocytosis. Further analyses suggested that coronin 1A prevented the lipidation-mediated sorting of the autophagy-related protein LC3 to the ruffled border and attenuated lysosome-plasma membrane fusion. In this process, the interactions between coronin 1A and actin were crucial. Collectively, our findings indicate that coronin 1A is a pivotal component that regulates lysosomal fusion and the secretion pathway in osteoclast-lineage cells and may provide a novel therapeutic target for bone diseases.

Web of Science ® 被引用回数 : 6

リンク情報
DOI
https://doi.org/10.1038/srep41710
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000396567700001&DestApp=WOS_CPL
ID情報
  • DOI : 10.1038/srep41710
  • ISSN : 2045-2322
  • Web of Science ID : WOS:000396567700001

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