EGF repeat-8 の Notch の突然変異は,Serrate/Jagged と Delta 家族のリガンドを区別する
Shinya Yamamoto1, Wu-Lin Charng, Nadia A Rana
1Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Science (New York, N.Y.)
|December 1, 2012
まとめ
ノッチ受容体の突然変異です.
科学分野:
- 発達生物学 発達生物学とは
- 細胞シグナル伝達 細胞信号伝達
- 分子遺伝学 分子遺伝学
背景:
- ノッチ・シグナリングは,発達に不可欠であり,がんや脳卒中などの疾患に関与しています.
- ノッチ受容体はリガンドデルタとセラートと相互作用するが,この選択性の分子基盤は不明である.
研究 の 目的:
- リンガンド選択性に関与するノッチ受容体の特定のドメインを特定する.
- ノッチ-リガンド差別の基礎となる分子機構を理解する.
主な方法:
- ドロソフィラの遺伝子スクリーンを利用して,ノッチ信号伝達に影響を与える変異を隔離しました.
- エピダーマルの成長因子リピート-8 (EGFr-8) のミスセンスの変異であるNotchの変異を特徴づけた.
- 変異したノッチ受容体のそのリガンドとの結合親和性を調査し,哺乳類のノッチ2.2における同類変異を調べた.
主要な成果:
- セルレート依存シグナル伝達が損なわれるが,デルタ依存シグナル伝達が損なわれないNotch (jigsaw) 変異を特定した.
- Notch (ノッチ) 変異は,EGFr-8のミスセンスの変異により,欠陥のあるセラート結合を引き起こす.
- 哺乳類のNotch2の同類変異は,Jagged1のシグナル伝達にも欠陥を示し,進化的保存を示した.
結論:
- EGFr-8内の進化的に保存されたバリン残基は,ノッチ受容体のリガンド選択性にとって不可欠である.
- この発見は,ノッチ-リガンド相互作用とノッチ依存シグナル伝達経路を理解するための分子基盤を提供します.
- 特定された突然変異は,ノッチに依存した様々な細胞プロセスや疾患を研究するための貴重なツールとして機能します.
関連する概念動画
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
01:19Cadherins in Tissue Organization
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Cell Sorting During Development
Cell sorting plays an...
Cell Sorting During Development
Cell sorting plays an...
02:33Hedgehog Signaling Pathway
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01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...