通过Eph受体的不同拼接形式调节排斥与粘附
J Holmberg1, D L Clarke, J Frisén
1Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden. jonas.frisen@cmb.ki.se
Nature
|November 23, 2000
概括
埃弗林-A5在胚胎发育中起着双重作用,调解细胞排斥和粘附. 它的缺失可能导致神经管缺陷,如由于神经融合失败而导致的无脑症.
科学领域:
- 发展生物学 发展生物学
- 细胞信号传递 细胞信号传递
- 分子生物学分子生物学
背景情况:
- 乙氨酸激酶受体和乙林联体对于发育过程中的细胞相互作用至关重要.
- 与Eph受体结合的联体通常会诱导氨酸酸化和细胞排斥.
- 神经管缺陷,如无脑症,突出了胚胎发育早期的关键过程.
研究的目的:
- 调查以弗林-A5在神经管关闭中的作用及其在细胞粘附中的潜在参与.
- 探索胚胎发育期间不同EphA7拼接变体的功能.
- 了解EphA7拼接变种如何影响细胞对以弗林信号的反应.
主要方法:
- 对表现出神经管缺陷的以弗林-A5无细胞小鼠的分析.
- 研究神经分泌过程中以弗林-A5和EphA7的共同表达模式.
- 研究不同EphA7拼接变体对细胞信号和行为 in vitro的影响.
主要成果:
- 埃弗林-A5无细胞小鼠显示神经管缺陷,特别是背部神经融合失败,表明在细胞粘附中发挥作用.
- 在神经发育过程中,Ephrin-A5与其受体EphA7在背部神经边缘共同表达.
- 截断的EphA7拼接变体抑制了全长的EphA7酸化,并在体外将细胞反应从排斥转变为粘附.
结论:
- 埃弗林-A5在神经发育期间有助于细胞粘附,除了它在细胞排斥中的已知作用外.
- EphA7的替代拼接产生了可以调节信号结果的变体,通过细胞粘附或排斥进行调解.
- 对于编排胚胎发育过程中的细胞行为而言,Eph受体氨酸激酶拼接变体的差异表达和功能至关重要.
相关概念视频
Alternative RNA Splicing
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
Receptor Downregulation in MVBs
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
Intracellular Signaling Affects Focal Adhesions
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...
Anchoring Junctions
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:...
Selectins
Cell adhesion is an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain, which...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
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.


