論文

査読有り
2014年10月

Targeting of aquaporin 4 into lipid rafts and its biological significance

BRAIN RESEARCH
  • Kunihiko Asakura
  • ,
  • Akihiro Ueda
  • ,
  • Sayuri Shima
  • ,
  • Tomomasa Ishikawa
  • ,
  • Chika Hikichi
  • ,
  • Seiko Hirota
  • ,
  • Takao Fukui
  • ,
  • Shinji Ito
  • ,
  • Tatsuro Mutoh

1583
開始ページ
237
終了ページ
244
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.brainres.2014.08.014
出版者・発行元
ELSEVIER SCIENCE BV

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system and is considered to be caused by the binding of NMO-IgG to aquaporin 4 (AQP4) on astrocytes, which initiates complement-dependent cytotoxicity. AQP4 has two isoforms, i.e., M1 and M23. AQP4 is considered to form heterotetramers containing both isoforms in vivo. Most of the previous studies were performed using either one of the isoforms expressing cell lines. In this study, we generated a fluorescent epitope-tagged AQP4 M1 and M23 co-expressing astrocyte cell line and examined the subcellular targeting of AQP4. In this cell line, AQP4 was targeted mostly to membrane lipid rafts fraction evidenced by sucrose density gradient ultracentrifugation followed by Western blotting with anti-AQP4 antibody. Cholesterol depletion with methyl-beta-cyclodextrin or simvastatin resulted in the dislocation (relocation) of AQP4 from lipid rafts to non-rafts fraction of the membrane and AQP4 was not internalized intracellularly. This change in the localization of AQP4 on membrane significantly reduced complement-dependent cytotoxic effects of NMO-IgG obtained from patients with NMO without affecting AQP4 orthogonal arrays. Thus, these data strongly suggest that the targeting of AQP4 in the lipid rafts is closely related to the pathogenic effects of NMO-IgG. (C) 2014 Elsevier B.V. All rights reserved.

Web of Science ® 被引用回数 : 1

リンク情報
DOI
https://doi.org/10.1016/j.brainres.2014.08.014
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000343357400022&DestApp=WOS_CPL

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