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Notch Signaling Pathway03:14

Notch Signaling Pathway

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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...
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Overview of Cell Death01:30

Overview of Cell Death

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Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
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The Extrinsic Apoptotic Pathway01:17

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The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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Structure of Cadherins01:25

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The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins”   is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This...
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Desmosomes01:05

Desmosomes

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The term desmosome derives from the Greek words "desmo" and "soma" meaning "adhesion bodies." This structure was first observed during the late 1800s and described as small, dense nodules in the epidermis. Desmosomes are button-like structures that help form an interlinked network of intermediate filaments across the cells. These junctions are  essential to hold cells together under mechanical stress and to maintain tissue integrity. Desmosomes are multi-protein...
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Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

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The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
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Assessing Signaling Properties of Ectodermal Epithelia During Craniofacial Development
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エクトodermal ディスプラジアの遺伝子欠陥は,開発における死亡領域アダプタを意味しています.

D J Headon1, S A Emmal, B M Ferguson

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, 77030, USA.

Nature
|January 10, 2002
PubMed
まとめ

研究者は,エダール受容体をシグナル伝達経路と結びつける重要なタンパク質であるエダラッドを特定しました. この発見は,低水素性皮膚外皮不形成症を説明し,発達中の保存されたシグナル伝達を強調しています.

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科学分野:

  • 発達生物学 発達生物学について
  • 分子遺伝学 分子遺伝学
  • 細胞シグナル伝達 細胞信号伝達

背景:

  • 死亡ドメインを持つ腫瘍死滅因子受容体 (TNFR) 家族のメンバーは,アダプタタンパク質を勧誘することによってシグナリングを開始します.
  • TNFRファミリーのタンパク質であるEDARは,髪,歯,皮膚外皮の発達に不可欠です.
  • エダールまたはそのリガンドエダの変異は,ヒトおよびマウスにおいて低水素性皮膚外皮不形成症 (HED) を引き起こします.

研究 の 目的:

  • エダール受容体に関連する死亡ドメインアダプタータンパク質を識別する.
  • HEDの基礎となる分子機構を明らかにする.
  • 開発中の死亡受容体/アダプターシグナリングの保存を調査する.

主な方法:

  • ネズミの折りたたみのある場所の遺伝子解析.
  • タンパク質相互作用の研究は,EdaraddがEdar.に結合することを確認する.
  • 人間のオートロジストの変異の特定 EDARADD.

主要な成果:

  • エダラード (Edar-associated death domain) が,折りたたまれた場所によってコード化されたアダプタータンパク質として識別された.
  • 折りたたまれた変異体は,エダールとエダの変異体と同一のHED現象型を示しています.
  • エダラードはエダルの死の領域と相互作用し,それを下流の信号伝達経路とリンクします.
  • 人間のEDARADDのミスセンス変異は,HEDを持つ家族で見つかりました.

結論:

  • エダラッドはエダール信号複合体の重要な構成要素であり,外皮の発達に不可欠です.
  • 発見は,死亡受容体/アダプタシグナルメカニズムが発達過程とアポプトシス過程の両方で保存されていることを示しています.
  • この研究は,低水分性エクトダーマ・ディスプラジアの遺伝的根拠に関する重要な洞察を提供します.