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

First Author  Itoh Y Year  2016
Journal  Proc Natl Acad Sci U S A Volume  113
Issue  21 Pages  E2955-64
PubMed ID  27170189 Mgi Jnum  J:233892
Mgi Id  MGI:5788349 Doi  10.1073/pnas.1516321113
Citation  Itoh Y, et al. (2016) PDK1-Akt pathway regulates radial neuronal migration and microtubules in the developing mouse neocortex. Proc Natl Acad Sci U S A 113(21):E2955-64
abstractText  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.
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