論文

査読有り 筆頭著者
2020年11月

A matricellular protein fibulin-4 is essential for the activation of lysyl oxidase

Science Advances
  • Kazuo Noda
  • ,
  • Kaori Kitagawa
  • ,
  • Takao Miki
  • ,
  • Masahito Horiguchi
  • ,
  • Tomoya O. Akama
  • ,
  • Takako Taniguchi
  • ,
  • Hisaaki Taniguchi
  • ,
  • Kazuaki Takahashi
  • ,
  • Yasumitsu Ogra
  • ,
  • Robert P. Mecham
  • ,
  • Masahiko Terajima
  • ,
  • Mitsuo Yamauchi
  • ,
  • Tomoyuki Nakamura

6
48
開始ページ
eabc1404
終了ページ
eabc1404
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1126/sciadv.abc1404
出版者・発行元
American Association for the Advancement of Science (AAAS)

Fibulin-4 is a matricellular protein required for extracellular matrix (ECM) assembly. Mice deficient in fibulin-4 (<italic>Fbln4−/−</italic>) have disrupted collagen and elastin fibers and die shortly after birth from aortic and diaphragmatic rupture. The function of fibulin-4 in ECM assembly, however, remains elusive. Here, we show that fibulin-4 is required for the activity of lysyl oxidase (LOX), a copper-containing enzyme that catalyzes the covalent cross-linking of elastin and collagen. LOX produced by <italic>Fbln4−/−</italic> cells had lower activity than LOX produced by wild-type cells due to the absence of lysine tyrosyl quinone (LTQ), a unique cofactor required for LOX activity. Our studies showed that fibulin-4 is required for copper ion transfer from the copper transporter ATP7A to LOX in the trans-Golgi network (TGN), which is a necessary step for LTQ formation. These results uncover a pivotal role for fibulin-4 in the activation of LOX and, hence, in ECM assembly.

リンク情報
DOI
https://doi.org/10.1126/sciadv.abc1404
URL
https://syndication.highwire.org/content/doi/10.1126/sciadv.abc1404

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