Xinxiang Key Laboratory of Neural Development, Stem Cells & Biotherapy Engineering Research Center of Henan, College of Life Science and Technology, Xinxiang Medical University, Xinxiang, 453003, China.
Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang, 453003, China.
J Mol Neurosci. 2019 Aug;68(4):539-548. doi: 10.1007/s12031-019-01316-w. Epub 2019 Apr 13.
Rap1 and N-cadherin regulate glia-independent translocation of cortical neurons. It remains unclear how Rap1 regulates N-cadherin-mediated neuronal migration. Here, we overexpressed Rap1gap in mouse brains (embryonic day 16) to inactivate Rap1, and observed that neurons did not migrate to the outer layer. We confirmed that Rap1 was involved in the regulation of late neurons in vivo. Rap1gap overexpression and Rap1 suppression in CHO cells decreased the expression of cytoskeletal proteins such as tubulin. Changes in the expression of cell morphology regulators, such as N-cadherin and β-catenin, were also observed. Inhibition of N-cadherin in mouse brains prevented neuronal migration to the outer layer. The morphology of CHO cells was changed after overexpression of Rap1gap. We propose that Rap1 regulates the expression of N-cadherin during embryonic development, which affects β-catenin expression. Beta-catenin in turn regulates cytoskeletal protein expression, ultimately affecting neuronal morphology and migration.
Rap1 和 N-钙黏蛋白调节皮质神经元的神经胶质非依赖性易位。Rap1 如何调节 N-钙黏蛋白介导的神经元迁移仍不清楚。在这里，我们在小鼠大脑（胚胎 16 天）中过表达 Rap1gap 以失活 Rap1，观察到神经元没有迁移到外层。我们证实 Rap1 参与了体内晚期神经元的调节。CHO 细胞中 Rap1gap 的过表达和 Rap1 的抑制降低了微管蛋白等细胞骨架蛋白的表达。还观察到细胞形态调节剂如 N-钙黏蛋白和 β-连环蛋白的表达变化。在小鼠脑中抑制 N-钙黏蛋白可防止神经元迁移到外层。Rap1gap 过表达后 CHO 细胞的形态发生改变。我们提出，Rap1 在胚胎发育过程中调节 N-钙黏蛋白的表达，这影响β-连环蛋白的表达。β-连环蛋白反过来调节细胞骨架蛋白的表达，最终影响神经元的形态和迁移。
