論文

国際誌
2019年1月23日

Drebrin-like (Dbnl) Controls Neuronal Migration via Regulating N-Cadherin Expression in the Developing Cerebral Cortex.

The Journal of neuroscience : the official journal of the Society for Neuroscience
  • Seika Inoue
  • ,
  • Kanehiro Hayashi
  • ,
  • Kyota Fujita
  • ,
  • Kazuhiko Tagawa
  • ,
  • Hitoshi Okazawa
  • ,
  • Ken-Ichiro Kubo
  • ,
  • Kazunori Nakajima

39
4
開始ページ
678
終了ページ
691
記述言語
英語
掲載種別
DOI
10.1523/JNEUROSCI.1634-18.2018
出版者・発行元
Journal of Neuroscience

The actin cytoskeleton is crucial for neuronal migration in the mammalian developing cerebral cortex. The adaptor protein Drebrin-like (Dbnl) plays important roles in reorganization of the actin cytoskeleton, dendrite formation, and endocytosis by interacting with F-actin, cobl, and dynamin. Although Dbnl is known to be expressed in the brain, the functions of this molecule during brain development are largely unknown. In this study, to examine the roles of Dbnl in the developing cerebral cortex, we conducted experiments using mice of both sexes with knockdown of Dbnl, effected by in utero electroporation, in the migrating neurons of the embryonic cortex. Time-lapse imaging of the Dbnl-knockdown neurons revealed that the presence of Dbnl is a prerequisite for appropriate formation of processes in the multipolar neurons in the multipolar cell accumulation zone or the deep part of the subventricular zone, and for neuronal polarization and entry into the cortical plate. We found that Dbnl knockdown decreased the amount of N-cadherin protein expressed on the plasma membrane of the cortical neurons. The defect in neuronal migration caused by Dbnl knockdown was rescued by moderate overexpression of N-cadherin and αN-catenin or by transfection of the phospho-mimic form (Y337E, Y347E), but not the phospho-resistant form (Y337F, Y347F), of Dbnl. These results suggest that Dbnl controls neuronal migration, neuronal multipolar morphology, and cell polarity in the developing cerebral cortex via regulating N-cadherin expression.SIGNIFICANCE STATEMENT Disruption of neuronal migration can cause neuronal disorders, such as lissencephaly and subcortical band heterotopia. During cerebral cortical development, the actin cytoskeleton plays a key role in neuronal migration; however, the mechanisms of regulation of neuronal migration by the actin cytoskeleton still remain unclear. Herein, we report that the novel protein Dbnl, an actin-binding protein, controls multiple events during neuronal migration in the developing mouse cerebral cortex. We also showed that this regulation is mediated by phosphorylation of Dbnl at tyrosine residues 337 and 347 and αN-catenin/N-cadherin, suggesting that the Dbnl-αN-catenin/N-cadherin pathway is important for neuronal migration in the developing cortex.

リンク情報
DOI
https://doi.org/10.1523/JNEUROSCI.1634-18.2018
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30504273
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343645
URL
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85060369194&origin=inward

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