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Axonal/Dendritic Growth and Circuit Formation

開催日 2014/9/12
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

A role for MAP7D1, a novel substrate of DCLK1, in axon elongation

  • P2-102
  • 古泉 博之 / Hiroyuki Koizumi:1 藤岡 洋美 / Hiromi Fujioka:2 富樫 和也 / Kazuya Togashi:1 岡田 康志 / Yasushi Okada:3 Gleeson Joseph G. / Joseph G. Gleeson:4 榎本 和生 / Kazuo Emoto:1 
  • 1:東京大院・理・生物科学・脳機能学分野 / Lab for Brain Function, Dept Biological Sciences, Grad School of Science, Univ of Tokyo, Japan 2:奈良先端大バイオサイエンス / Nara Institute of Science and Technology, Nara, Japan 3:理研QBiC・細胞極性統御 / Lab for Cell Polarity Regulation, Quantitative Biology Center RIKEN, Osaka, Japan 4:Neurogenetics Lab, HHMI / Dept Neuroscience, Univ of California San Diego, USA / Neurogenetics Lab, HHMI / Dept Neuroscience, Univ of California San Diego, USA 

Doublecortin-like kinase 1 (DCLK1) is a unique serine-threonine protein kinase that has a microtubule-binding domain in its N-terminal. Targeted disruption of Dclk1 in mice resulted in impaired axonal elongation in the corpus callosum. In addition, further depletion of doublecortin (DCX), a paralog of DCLK1, in Dclk1 knockout mice resulted in severe cortical lamination defects. These results suggested that DCLK1 functions in cortical neuronal migration and axon elongation during brain development.
The N-terminal microtubule-binding domain has been shown to contribute to neuronal migration and neurite outgrowth through regulating microtubule bundling and stabilization, however the function of the protein kinase domain remains elusive. To further understand the role of the DCLK1 kinase domain during brain development, we identified a MAP7D1 (microtubule-associated protein 7 domain containing 1) as a novel in vitro substrate of DCLK1. miRNA-mediated knockdown of MAP7D1 in cortical layer 2/3 pyramidal cells resulted in impaired callosal axon elongation (40% decrease). Overexpression of unphosphorylated mutant MAP7D1, but not wild-type MAP7D1, also impaired callosal axon elongation (40% decrease). Furthermore, we found that MAP7D1 interacted with kinesin-1 motor protein and the deletion of this interacting-domain of unphosphorylated mutant no more impaired the axon elongation. We also found that MAP7D1 / DCX double knockdown in cortical neurons caused no significant radial migration defects in contrast to the migration defects caused by DCLK1 / DCX double knockdown. We concluded that MAP7D1 phosphorylation by DCLK1 plays a role in axon elongation through interacting with kinesin-1 motor protein, but has no major role in neuronal migration.

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