PDK1-Akt pathway regulates radial neuronal migration and microtubules in the developing mouse neocortex

Yasuhiro Itoh, Maiko Higuchi, Koji Oishi, Yusuke Kishi, Tomohiko Okazaki, Hiroshi Sakai, Takaki Miyata, Kazunori Nakajima, Yukiko Gotoh

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Neurons migrate a long radial distance by a process known as locomotion in the developing mammalian neocortex. During locomotion, immature neurons undergo saltatory movement along radial glia fibers. The molecular mechanisms that regulate the speed of locomotion are largely unknown. We now show that the serine/ threonine kinase Akt and its activator phosphoinositide-dependent protein kinase 1 (PDK1) regulate the speed of locomotion of mouse neocortical neurons through the cortical plate. Inactivation of the PDK1-Akt pathway impaired the coordinated movement of the nucleus and centrosome, a microtubule-dependent process, during neuronal migration. Moreover, the PDK1-Akt pathway was found to control microtubules, likely by regulating the binding of accessory proteins including the dynactin subunit p150glued . Consistent with this notion, we found that PDK1 regulates the expression of cytoplasmic dynein intermediate chain and light intermediate chain at a posttranscriptional level in the developing neocortex. Our results thus reveal an essential role for the PDK1-Akt pathway in the regulation of a key step of neuronal migration.

Original languageEnglish
Pages (from-to)E2955-E2964
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number21
DOIs
Publication statusPublished - 2016 May 24

Keywords

  • Dynein
  • Microtubule
  • Neocortex
  • Neuronal migration
  • PDK1-Akt pathway

ASJC Scopus subject areas

  • General

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