DCC-Mediated Dab1 Phosphorylation Participates in the Multipolar-to-Bipolar Transition of Migrating Neurons

Jian Hua Zhang, Yi Fei Zhao, Xiao Xiao He, Yang Zhao, Zi Xuan He, Lei Zhang, Ying Huang, Yu Bing Wang, Ling Hu, Lin Liu, Hua Li Yu, Jia Hui Xu, Ming Ming Lai, Dong Dong Zhao, Lei Cui, Wei Xiang Guo, Wencheng Xiong, Yu Qiang Ding, Xiao Juan Zhu

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Newborn neurons undergo inside-out migration to their final destinations during neocortical development. Reelin-induced tyrosine phosphorylation of disabled 1 (Dab1) is a critical mechanism controlling cortical neuron migration. However, the roles of Reelin-independent phosphorylation of Dab1 remain unclear. Here, we report that deleted in colorectal carcinoma (DCC) interacts with Dab1 via its P3 domain. Netrin 1, a DCC ligand, induces Dab1 phosphorylation at Y220 and Y232. Interestingly, knockdown of DCC or truncation of its P3 domain dramatically delays neuronal migration and impairs the multipolar-to-bipolar transition of migrating neurons. Notably, the migration delay and morphological transition defects are rescued by the expression of a phospho-mimetic Dab1 or a constitutively active form of Fyn proto-oncogene (Fyn), a member of the Src-family tyrosine kinases that effectively induces Dab1 phosphorylation. Collectively, these findings illustrate a DCC-Dab1 interaction that ensures proper neuronal migration during neocortical development. Non-Reelin-induced Dab1 phosphorylation was previously identified, but not characterized. Zhang et al. find that DCC interacts with Dab1, and DCC-mediated signaling effectively induces Dab1 phosphorylation. The DCC/Dab1 signaling complex is essential for neuronal migration, especially during the multipolar-to-bipolar transition.

Original languageEnglish (US)
Pages (from-to)3598-3611
Number of pages14
JournalCell Reports
Volume22
Issue number13
DOIs
StatePublished - Mar 27 2018

Keywords

  • DCC
  • Dab1
  • Fyn
  • Reelin
  • morphological transition
  • neocortex development
  • netrin 1
  • neuronal migration
  • tyrosine phosphorylation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Zhang, J. H., Zhao, Y. F., He, X. X., Zhao, Y., He, Z. X., Zhang, L., Huang, Y., Wang, Y. B., Hu, L., Liu, L., Yu, H. L., Xu, J. H., Lai, M. M., Zhao, D. D., Cui, L., Guo, W. X., Xiong, W., Ding, Y. Q., & Zhu, X. J. (2018). DCC-Mediated Dab1 Phosphorylation Participates in the Multipolar-to-Bipolar Transition of Migrating Neurons. Cell Reports, 22(13), 3598-3611. https://doi.org/10.1016/j.celrep.2018.03.005