Magnesium absorption by MagEx

• Project/Area Number: 24657090
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: Osaka University
• Principal Investigator: FUNATO Yosuke 大阪大学, 微生物病研究所, 助教 (60505775)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 膜輸送と輸送タンパク質 / マグネシウム / 恒常性 / トランスポーター / 局在制御 / MagEx

Research Abstract

Transcellular Mg2+ transport across epithelia is essential for magnesium homeostasis. Apical entry and basolateral extrusion is required to accomplish this process, but molecules responsible for basolateral extrusion have not yet been identified. I perform functional analyses of uncharacterized membrane protein MagEx. Live imaging analyses reveal that MagEx can extrude Mg2+ by exchanging intracellular Mg2+ with extracellular Na+. Immunohistochemical analyses show that MagEx is strongly expressed in intestinal epithelia, and localizes to their basolateral membrane. To clarify the in vivo role of MagEx, its knockout mice was generated. Homozygotes show hypomagnesemia, and intestinal absorption of magnesium is impaired in these mice. These results show that MagEx is the basolaterally located Mg2+ extrusion molecule, and demonstrate the crucial importance of Mg2+ extrusion by MagEx in magnesium homeostasis.

Research Products

• [Journal Article] Reversible oxidation of PRL family protein-tyrosine phosphatases (2014)
  • Author(s): Funato, Y. and Miki, H.
  • Journal Title: Methods Volume: 65 Issue: 2 Pages: 184-189
  • DOI: 10.1016/j.ymeth.2013.06.032
  • Peer Reviewed
• [Journal Article] Basolateral Mg2+ extrusion via CNNM4 mediates transcellular Mg2+ transport across epithelia: a mouse model (2013)
  • Author(s): Daisuke Yamazaki, Yosuke Funato, Jiro Miura, Sunao Sato, Satoru Toyosawa, Kazuharu Furutani, Yoshihisa Kurachi, Yoshihiro Omori, Takahisa Furukawa, Tetsuya Tsuda, Susumu Kuwabata, Shin Mizukami, Kazuya Kikuchi, Hiroaki Miki
  • Journal Title: PLoS Genetics Volume: 9(12) Issue: 12 Pages: e1003983-e1003983
  • DOI: 10.1371/journal.pgen.1003983
  • Peer Reviewed
• [Journal Article] Nucleoredoxin regulates glucose metabolism via phosphofructokinase 1 (2013)
  • Author(s): Funato, Y
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 440 Issue: 4 Pages: 737-742
  • DOI: 10.1016/j.bbrc.2013.09.138
  • Peer Reviewed
• [Journal Article] Thioredoxin-related protein 32 (TRP32) specifically reduces oxidized phosphatase of regenerating liver (PRL) (2013)
  • Author(s): Ishii, T., Funato, Y., and Miki, H.
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 10 Pages: 7263-7270
  • DOI: 10.1074/jbc.m112.418004
  • Peer Reviewed
• [Presentation] マグネシウム排出分子MagExとがん転移 (2014)
  • Author(s): 船戸洋佑、山崎大輔、三木裕明
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-03-16
• [Presentation] 蛋白質の可逆的な酸化修飾を介したシグナル伝達の制御 (2012)
  • Author(s): 船戸洋佑、三木裕明
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-15