PACT/RAX Regulates the Migration of Cerebellar Granule Neurons in the Developing Cerebellum

PACT and its murine ortholog RAX were originally identified as a protein activator for the dsRNA-dependent, interferon-inducible protein kinase PKR. Recent studies indicated that RAX played a role in embryogenesis and neuronal development. In this study, we investigated the expression of RAX during...

Descripción completa

Detalles Bibliográficos
Autores principales: Yong, Yue, Meng, Ya, Ding, Hanqing, Fan, Zhiqin, Tang, Yifen, Zhou, Chenghua, Luo, Jia, Ke, Zun-Ji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302322/
https://www.ncbi.nlm.nih.gov/pubmed/25609658
http://dx.doi.org/10.1038/srep07961
_version_ 1782353778180096000
author Yong, Yue
Meng, Ya
Ding, Hanqing
Fan, Zhiqin
Tang, Yifen
Zhou, Chenghua
Luo, Jia
Ke, Zun-Ji
author_facet Yong, Yue
Meng, Ya
Ding, Hanqing
Fan, Zhiqin
Tang, Yifen
Zhou, Chenghua
Luo, Jia
Ke, Zun-Ji
author_sort Yong, Yue
collection PubMed
description PACT and its murine ortholog RAX were originally identified as a protein activator for the dsRNA-dependent, interferon-inducible protein kinase PKR. Recent studies indicated that RAX played a role in embryogenesis and neuronal development. In this study, we investigated the expression of RAX during the postnatal development of the mouse cerebellum and its role in the migration of cerebellar granule neurons (CGNs). High expression of RAX was observed in the cerebellum from postnatal day (PD) 4 to PD9, a period when the CGNs migrate from the external granule layer (EGL) to the internal granule layer (IGL). The migration of the EGL progenitor cells in vivo was inhibited by RAX knockdown on PD4. This finding was confirmed by in vitro studies showing that RAX knockdown impaired the migration of CGNs in cerebellar microexplants. PACT/RAX-regulated migration required its third motif and was independent of PKR. PACT/RAX interacted with focal adhesion kinase (FAK) and PACT/RAX knockdown disturbed the FAK phosphorylation in CGNs. These findings demonstrated a novel function of PACT/RAX in the regulation of neuronal migration.
format Online
Article
Text
id pubmed-4302322
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-43023222015-01-27 PACT/RAX Regulates the Migration of Cerebellar Granule Neurons in the Developing Cerebellum Yong, Yue Meng, Ya Ding, Hanqing Fan, Zhiqin Tang, Yifen Zhou, Chenghua Luo, Jia Ke, Zun-Ji Sci Rep Article PACT and its murine ortholog RAX were originally identified as a protein activator for the dsRNA-dependent, interferon-inducible protein kinase PKR. Recent studies indicated that RAX played a role in embryogenesis and neuronal development. In this study, we investigated the expression of RAX during the postnatal development of the mouse cerebellum and its role in the migration of cerebellar granule neurons (CGNs). High expression of RAX was observed in the cerebellum from postnatal day (PD) 4 to PD9, a period when the CGNs migrate from the external granule layer (EGL) to the internal granule layer (IGL). The migration of the EGL progenitor cells in vivo was inhibited by RAX knockdown on PD4. This finding was confirmed by in vitro studies showing that RAX knockdown impaired the migration of CGNs in cerebellar microexplants. PACT/RAX-regulated migration required its third motif and was independent of PKR. PACT/RAX interacted with focal adhesion kinase (FAK) and PACT/RAX knockdown disturbed the FAK phosphorylation in CGNs. These findings demonstrated a novel function of PACT/RAX in the regulation of neuronal migration. Nature Publishing Group 2015-01-22 /pmc/articles/PMC4302322/ /pubmed/25609658 http://dx.doi.org/10.1038/srep07961 Text en Copyright © 2015, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Yong, Yue
Meng, Ya
Ding, Hanqing
Fan, Zhiqin
Tang, Yifen
Zhou, Chenghua
Luo, Jia
Ke, Zun-Ji
PACT/RAX Regulates the Migration of Cerebellar Granule Neurons in the Developing Cerebellum
title PACT/RAX Regulates the Migration of Cerebellar Granule Neurons in the Developing Cerebellum
title_full PACT/RAX Regulates the Migration of Cerebellar Granule Neurons in the Developing Cerebellum
title_fullStr PACT/RAX Regulates the Migration of Cerebellar Granule Neurons in the Developing Cerebellum
title_full_unstemmed PACT/RAX Regulates the Migration of Cerebellar Granule Neurons in the Developing Cerebellum
title_short PACT/RAX Regulates the Migration of Cerebellar Granule Neurons in the Developing Cerebellum
title_sort pact/rax regulates the migration of cerebellar granule neurons in the developing cerebellum
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302322/
https://www.ncbi.nlm.nih.gov/pubmed/25609658
http://dx.doi.org/10.1038/srep07961
work_keys_str_mv AT yongyue pactraxregulatesthemigrationofcerebellargranuleneuronsinthedevelopingcerebellum
AT mengya pactraxregulatesthemigrationofcerebellargranuleneuronsinthedevelopingcerebellum
AT dinghanqing pactraxregulatesthemigrationofcerebellargranuleneuronsinthedevelopingcerebellum
AT fanzhiqin pactraxregulatesthemigrationofcerebellargranuleneuronsinthedevelopingcerebellum
AT tangyifen pactraxregulatesthemigrationofcerebellargranuleneuronsinthedevelopingcerebellum
AT zhouchenghua pactraxregulatesthemigrationofcerebellargranuleneuronsinthedevelopingcerebellum
AT luojia pactraxregulatesthemigrationofcerebellargranuleneuronsinthedevelopingcerebellum
AT kezunji pactraxregulatesthemigrationofcerebellargranuleneuronsinthedevelopingcerebellum