RIPK4-IRF6信号軸は,表皮の分化とバリア機能を保護する
Nina Oberbeck1, Victoria C Pham2, Joshua D Webster3
1Department of Physiological Chemistry, Genentech, South San Francisco, CA, USA.
Nature
|October 4, 2019
まとめ
キナーゼRIPK4と転写因子IRF6は,表皮のバリア機能に不可欠です. 皮膚の正常な発達を保証し 欠陥は重度の発達異常につながる
科学分野:
- 発達生物学
- 分子生物学
- 遺伝学
背景:
- 哺乳類の表皮の整合性は 幹細胞の増殖と分化に依存しています
- RIPK4とIRF6の変異は,表皮の欠陥を持つ発達症候群を引き起こす.
- RIPK4とIRF6が表皮の分化に果たす正確な役割は完全に理解されていません.
研究 の 目的:
- RIPK4 と IRF6 が表皮分化を調節するメカニズムを解明する.
- 開発中の表皮にIRF6によって制御される転写プログラムを定義する.
- IRF6欠乏が表皮壁形成に及ぼす機能的影響を理解する.
主な方法:
- 野生型およびIRF6欠乏したマウス胚にRNA配列決定 (RNA-seq),ChIP-seq,およびATAC-seqを用いた.
- 開発中のRIPK4のキナーゼ活性要件を調査した.
- 活性化に重要なIRF6のリン酸化部位を分析した.
主要な成果:
- RIPK4キナーゼの活動はマウスの発達に不可欠です.
- RIPK4とIRF6は,表皮における一般的な生物学的プロセスを調節する.
- セル413とセル424でIRF6のリン酸化により活性化されます.
- IRF6欠乏症は,脂質代謝と緊密な結合形成に関与する遺伝子を損なう.
- IRF6−−マウスは角層の脂質組成と表皮壁の欠陥を示している.
結論:
- RIPK4とIRF6は,調整された分化制御によって表皮の整合性の主要な調節剤である.
- RIPK4-IRF6軸の欠陥は,耳面,皮膚,生殖器の発達に影響する発達症候群を説明します.
- IRF6のリン酸化は,表皮の発達中の活性化経路における重要なステップです.
関連する概念動画
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.6K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.6K
Renewal of Skin Epidermal Stem Cells
2.9K
The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular...
2.9K
Regulation of the Unfolded Protein Response
2.9K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.9K
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.4K
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...
2.4K
MAPK Signaling Cascades
7.8K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.8K
Cell Signaling in Plants
6.1K
Plant cells communicate to coordinate their cycle of growth, flowering and fruiting, and activities in roots, shoots, and leaves in response to the changing environmental conditions. Plant signaling is distinct from animal signaling. Plants primarily utilize enzyme-linked receptors, whereas the largest class of cell-surface receptors in animals are G-protein coupled receptors (GPCRs). Unlike animals, receptor tyrosine kinases are rare in plants. Instead, plants have a diverse class of...
6.1K


