ディストログリカンの上のLARGEグリカンは,ダイストロフィーを防ぐために調節可能なマトリックス・スキャフォルドとして機能します
Matthew M Goddeeris1, Biming Wu, David Venzke
11] Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, USA [2] Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, USA.
Nature
|October 18, 2013
まとめ
ディストログリカンのLARGE-グリカン鎖の長さは,骨格筋の機能に極めて重要です. これらの鎖を拡張すると,細胞外マトリックス結合が強化され,筋縮が予防されます.
科学分野:
- 細胞生物学 細胞生物学
- バイオケミストリー バイオケミストリー
- 発達生物学 発達生物学について
背景:
- 細胞表面のグリカンコートは,細胞機能に不可欠であり,非常にダイナミックです.
- アセチルグルコサミニルトランスフェラーゼのような酵素 (LARGE) は,その細胞外マトリックス受容体機能に不可欠なダイストログリカンに,繰り返すポリサッカリド単位 (LARGE-グリカン) を追加します.
- LARGE-グリカンの欠陥は筋縮を引き起こすが,グリカン鎖の長さの正確な役割は不明である.
研究 の 目的:
- LARGE-グリカンリピートの細胞機能と,筋肉縮との相関を調査する.
- LARGE-グリカン鎖の拡張がディストログリカンの細胞外マトリックス結合能力にどのように影響するかを決定する.
- 骨格筋の発達と再生におけるLARGE-グリカンの役割を明らかにする.
主な方法:
- マウス筋肉の差異化におけるLargeとディストログリカンの調整アップを研究した.
- 合成されたLARGE-グリカンリピートを使用して,細胞外マトリックスリガンドとの結合能力を評価しました.
- ブロックされた マウスの筋肉再生中の大きなアップレギュレーションで,ディストログリカンと筋肉機能への影響を観察する.
主要な成果:
- Largeとdystroglycanの調整されたアップレギュレーションは,LARGE-glycan鎖の急速な拡張を促進します.
- LARGE-グリカン鎖の長さの増加は,細胞外マトリックスリガンドへの結合の強化と直接相関しています.
- ブロック 筋肉再生中の大きなアップレギュレーションは,LARGE-glycanを減少させ,基礎膜の欠陥,不成熟な神経筋結節,筋肉機能障害を引き起こす.
- 重度の筋縮症の患者は,LARGE-グリカンのリピート数が少ない.
結論:
- ディストログリカン上のLARGE-グリカンは,細胞外マトリックスタンパク質の調節可能な支架として作用します.
- LARGE-グリカン鎖の拡張は,正常な骨格筋の機能と完全性にとって不可欠です.
- 機能不全のLARGE-グリカン拡張は,筋ジストロフィーの病原化に寄与する.
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