Mfsd2bは,赤血球と血小板におけるスフィンゴシン-1-リン酸の輸出に不可欠である
Thiet M Vu1, Ayako-Nakamura Ishizu2, Juat Chin Foo3
1Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 5 Medical Drive, Singapore 117545.
Nature
|October 19, 2017
まとめ
メジャーファシリテータースーパーファミリートランスポーター2b (Mfsd2b) は,赤血球と血小板からのスフィンゴシン-1-リン酸 (S1P) の主要な輸出者であり,プラズマのS1Pレベルと赤血球の形態に影響を与える.
科学分野:
- 脂質シグナリング
- 血液学
- 分子輸送
背景:
- スフィンゴシン-1-リン酸 (S1P) は,多様な生物学的機能を持つ重要なシグナリング脂質である.
- 特に赤血球と血小板からのS1P分泌に責任のある細胞輸出者は特定されなかった.
- S1Pの輸出を理解することは,生理学と病気におけるその役割を解読するために極めて重要です.
研究 の 目的:
- 赤血球と血小板からスフィンゴシン-1-リン酸 (S1P) の輸出を担当するトランスポーターを特定する.
- S1P輸出障害の生理学的影響を in vivoで調査する.
- 赤血球の健康と形態におけるS1P分泌の役割を明らかにする.
主な方法:
- Mfsd2b ノックアウトマウスの生成と分析
- 赤血球,血小板,血の総合的な脂質分析
- Mfsd2bのS1P輸送活動を確認するための生化学的測定.
- アナフィラキシーショックとストレスエリトポエーゼを含む生理学的反応の評価
主要な成果:
- Mfsd2bのノックアウト赤血球と血小板は,S1P種の特定の蓄積を示した.
- Mfsd2bは生化学的測定と in vivo で S1P のアクティブエクスポーターとして確認されました.
- Mfsd2b ノックアウトマウスでは血S1P濃度が42~54%低下した.
- Mfsd2b欠乏症は,アナフィラキシーショックに対する感受性の高まりと,ストレス下での赤血球の形態の障害を引き起こした.
結論:
- 孤児伝達体Mfsd2bは,赤血球と血小板からスフィンゴシン-1-リン酸 (S1P) の輸出に不可欠である.
- Mfsd2bは循環中のS1Pの大部分を占め,全身のS1Pレベルに影響を与えています.
- Mfsd2b媒介のS1P分泌は赤血球の整体性と形態の維持に不可欠であり,スフィンゴリピド代謝における新たな役割を明らかにしている.
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