The Mechanism of Rap1 Regulates N-cadherin to Control Neuronal Migration

J Mol Neurosci. 2019 Aug;68(4):539-548. doi: 10.1007/s12031-019-01316-w. Epub 2019 Apr 13.

Abstract

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.

Keywords: In utero electroporation; Mouse; N-cadherin; Neuron migration; Rap1.

MeSH terms

  • Animals
  • CHO Cells
  • Cadherins / metabolism*
  • Cell Movement*
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology
  • Cerebral Cortex / metabolism
  • Cricetinae
  • Cricetulus
  • Mice
  • Mice, Inbred C57BL
  • Neurons / metabolism*
  • Neurons / physiology
  • Tubulin / genetics
  • Tubulin / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism
  • rap1 GTP-Binding Proteins / genetics
  • rap1 GTP-Binding Proteins / metabolism*

Substances

  • Cadherins
  • Tubulin
  • beta Catenin
  • Rap1 protein, mouse
  • rap1 GTP-Binding Proteins