Loss of ephrin-A5 function disrupts lens fiber cell packing and leads to cataract
Loss of ephrin-A5 function disrupts lens fiber cell packing and leads to cataract
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DOI：
10.1073/pnas.0808987105
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发表时间：
2008-10-28
影响因子：
11.1
通讯作者：
Zhou, Renping
中科院分区：
文献类型：
--
作者：
Cooper, Margaret A.;Son, Alexander I.;Zhou, Renping
细胞-细胞相互作用将透镜纤维细胞组织成高度有序的结构以保持透明度。然而，调节这种相互作用的信号尚未得到很好的表征。我们在这里报告，ephrin-A5，Eph受体酪氨酸激酶的配体，在透镜纤维细胞形状和细胞-细胞相互作用中起着关键作用。缺乏肝配蛋白-A5功能的小鼠的透镜纤维细胞在横截面上呈现圆形和不规则，与WT晶状体中它们的正常六边形外观形成对比。白内障最终在87%的ephrin-A5 KO小鼠中发展。我们进一步证明，肝配蛋白-A5与EphA 2受体相互作用，通过增强β-连环蛋白向N-钙粘蛋白的募集来调节粘附连接复合物。这些结果表明Eph受体及其配体是透镜发育和维持的关键调节剂。
Cell-cell interactions organize lens fiber cells into highly ordered structures to maintain transparency. However, signals regulating such interactions have not been well characterized. We report here that ephrin-A5, a ligand of the Eph receptor tyrosine kinases, plays a key role in lens fiber cell shape and cell-cell interactions. Lens fiber cells in mice lacking ephrin-A5 function appear rounded and irregular in cross-section, in contrast to their normal hexagonal appearance in WT lenses. Cataracts eventually develop in 87% of ephrin-A5 KO mice. We further demonstrate that ephrin-A5 interacts with the EphA2 receptor to regulate the adherens junction complex by enhancing recruitment of beta-catenin to N-cadherin. These results indicate that the Eph receptors and their ligands are critical regulators of lens development and maintenance.