Phosphorylation of CRMP2 is required for migration and positioning of Purkinje cells: Redundant roles of CRMP1 and CRMP4

Yuki Yamazaki, Jun Nagai, Satoshi Akinaga, Yumeno Koga, Masaya Hasegawa, Miyuki Takahashi, Naoya Yamashita, Papachan Kolattukudy, Yoshio Goshima, Toshio Ohshima

Research output: Contribution to journalArticle

Abstract

Proper migration and positioning of Purkinje cells are important for formation of the developing cerebellum. Although several cyclin-dependent kinase 5 (Cdk5) substrates are known to be critical for ordered neuronal migration, there are no reports of mutant mouse-based, in vivo studies on the function of Cdk5-phosphorylation substrates in migration of Purkinje cells. We focused on the analysis of collapsin response mediator protein 2 (CRMP2), one of the Cdk5 substrates, because a previous study reported migration defects of cortical neurons with shRNA-mediated knockdown of CRMP2. However, CRMP2 KI/KI mice, in which Cdk5-phosphorylation is inhibited, showed little defects in Purkinje cell migration and positioning. We hypothesized compensatory redundant functions of the other CRMPs, and analyzed the migration and positioning of Purkinje cells in the cerebellum in every combination of CRMP1 knockout (KO), CRMP2 KI/KI, and CRMP4 KO mice. Severe disturbance of migration and positioning of Purkinje cells were observed in the triple mutant mice. We also found motor coordination defects in the triple CRMPs mutant mice. These results suggest the importance of both, phosphorylation of CRMP2 by Cdk5 and the redundant functions of CRMP1 and CRMP4 in proper migration and positioning of Purkinje cells in developing cerebellum.

Original languageEnglish
Article number146762
JournalBrain Research
Volume1736
DOIs
Publication statusPublished - 2020 Jun 1

Keywords

  • Cerebellum
  • Neuronal migration
  • Phosphorylation
  • Purkinje cell

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Phosphorylation of CRMP2 is required for migration and positioning of Purkinje cells: Redundant roles of CRMP1 and CRMP4'. Together they form a unique fingerprint.

  • Cite this

    Yamazaki, Y., Nagai, J., Akinaga, S., Koga, Y., Hasegawa, M., Takahashi, M., Yamashita, N., Kolattukudy, P., Goshima, Y., & Ohshima, T. (2020). Phosphorylation of CRMP2 is required for migration and positioning of Purkinje cells: Redundant roles of CRMP1 and CRMP4. Brain Research, 1736, [146762]. https://doi.org/10.1016/j.brainres.2020.146762