介酶转胺酶2激活表皮ADAM17:与G蛋白结合受体56 (ADGRG1) 信号连接
Lea Bauer1, Jessica Edwards1, Andreas Heil1
1College of Biomedical and Life Sciences, School of Dentistry, Cardiff University, Cardiff CF14 4XY, UK.
International journal of molecular sciences
|February 24, 2024
概括
介质细胞矩阵相关的转胺酶2 (TG2) 结合GPR56,激活了关键的角质细胞迁移,对伤口愈合至关重要. 这种相互作用涉及RhoA和EGFR信号,突出了皮肤修复的新治疗点.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 皮肤病学 皮肤病学
背景情况:
- 介质细胞矩阵相关的转氨酶2 (TG2) 在伤口愈合期间在状细胞再上皮质化中发挥作用.
- TG2通过激活分解素和金属蛋白酶17 (ADAM17) 影响了角质细胞迁移.
研究的目的:
- 阐明TG2在角质细胞再上皮质化中的作用.
- 调查TG2与附G蛋白结合受体GPR56在角质细胞迁移中的相互作用.
主要方法:
- 创伤愈合模型的开发.
- 在TG2阳性和TG2无条件下评估角质细胞迁移.
- 路西法酶记者测试测量TG2的ADAM17激活和GPR56激活.
- 分析TG2和GPR56内分细胞和结合动力学.
主要成果:
- ADAM17的TG2激活导致EGFR的交换激活和在TG2-阳性细胞外基质 (ECM) 上的角质细胞迁移.
- 在TG2零条件下,角质细胞迁移受损.
- TG2激活GPR56,一种被提议的TG2受体,以一种依赖于N端GPR56域和TG2β-桶域的方式.
- TG2-GPR56的相互作用涉及RhoA和ADAM17的激活,并导致EGFR的交换激活.
- TG2 与 N-终端 GPR56 域结合,只有支持的 TG2 形态表现出关联.
结论:
- TG2和GPR56形成一个联体受体对,通过RhoA和EGFR的交换激活驱动状细胞迁移.
- 这种相互作用对于在伤口愈合过程中有效的再上皮质化至关重要.
- 准TG2-GPR56通路可能为增强皮肤修复提供治疗策略.
相关概念视频
Intracellular Signaling Affects Focal Adhesions
2.7K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.7K
TGF - β Signaling Pathway
7.4K
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...
7.4K
Tension Response at Adherens Junctions
2.6K
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
2.6K
Cell-matrix's Response to Mechanical Forces
2.6K
In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue.
Anchoring junctions mechanically attach a cell to the...
Anchoring junctions mechanically attach a cell to the...
2.6K
Anchoring Junctions
3.8K
Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...
3.8K
Adherens Junctions
4.8K
Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types – adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
Adherens Junctions are Dynamic
Adherens Junctions are Dynamic
4.8K


