Xu Q, Mellitzer G, Wilkinson D G
Division of Developmental Neurobiology, National Institute for Medical Research, London, UK.
Philos Trans R Soc Lond B Biol Sci. 2000 Jul 29;355(1399):993-1002. doi: 10.1098/rstb.2000.0635.
Eph receptor tyrosine kinases and their membrane-bound ligands, ephrins, have key roles in patterning and morphogenesis. Interactions between these molecules are promiscuous, but largely fall into two groups: EphA receptors bind to glycosylphosphatidyl inositol-anchored ephrin-A ligands, and EphB receptors bind to transmembrane ephrin-B proteins. Ephrin-B proteins transduce signals, such that bidirectional signalling can occur upon interaction with the Eph receptor. In many tissues, there are complementary and overlapping expression domains of interacting Eph receptors and ephrins. An important role of Eph receptors and ephrins is to mediate cell contact-dependent repulsion, and this has been implicated in the pathfinding of axons and neural crest cells, and the restriction of cell intermingling between hindbrain segments. Studies in an in vitro system show that bidirectional activation is required to prevent intermingling between cell populations, whereas unidirectional activation can restrict cell communication via gap junctions. Recent work indicates that Eph receptors can also upregulate cell adhesion, but the biochemical basis of repulsion versus adhesion responses is unclear. Eph receptors and ephrins have thus emerged as key regulators that, in parallel with cell adhesion molecules, underlie the establishment and maintenance of patterns of cellular organization.
Eph受体酪氨酸激酶及其膜结合配体—— Ephrin，在模式形成和形态发生中起关键作用。这些分子之间的相互作用是混杂的，但大致可分为两类：EphA受体与糖基磷脂酰肌醇锚定的Ephrin - A配体结合，而EphB受体与跨膜Ephrin - B蛋白结合。Ephrin - B蛋白可转导信号，因此与Eph受体相互作用时可发生双向信号传导。在许多组织中，相互作用的Eph受体和Ephrin存在互补和重叠的表达域。Eph受体和Ephrin的一个重要作用是介导细胞接触依赖性排斥，这与轴突和神经嵴细胞的路径寻找以及后脑节段间细胞混合的限制有关。体外系统研究表明，双向激活是防止细胞群体混合所必需的，而单向激活可通过间隙连接限制细胞通讯。最近的研究表明，Eph受体也可上调细胞黏附，但排斥与黏附反应的生化基础尚不清楚。因此，Eph受体和Ephrin已成为关键调节因子，与细胞黏附分子一起，构成细胞组织结构模式建立和维持的基础。
