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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group
2015
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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 |
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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 |
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