title: PDK1-Akt pathway regulates radial neuronal migration and microtubules in the developing mouse neocortex.
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 p150(glued) 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan; Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan; yasuhiro.m.itoh@gmail.com.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Itoh
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan; Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan;
authors.forename: Maiko
authors.initials: M
authors.lastname: Higuchi
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan;
authors.forename: Koji
authors.initials: K
authors.lastname: Oishi
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan; Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan;
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kishi
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan; Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan;
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Okazaki
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan; Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan;
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakai
authors.affiliation: Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Takaki
authors.initials: T
authors.lastname: Miyata
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan;
authors.forename: Kazunori
authors.identifier: 0000-0003-1864-9425
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan; Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan;
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Gotoh
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D000072159:Dynactin Complex / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D019579:Neocortex / Q000166:cytology / Q000254:growth & development*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C000606364:Dctn1 protein, mouse; D000072159:Dynactin Complex; C000631433:Pdk1 protein, mouse; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: PDK1–Akt pathway; dynein; microtubule; neocortex; neuronal migration