PACT/RAX regulates the migration of cerebellar granule neurons in the developing cerebellum

Yue Yong; Ya Meng; Hanqing Ding; Zhiqin Fan; Yifen Tang; Chenghua Zhou; Jia Luo; Zun-Ji Ke

doi:10.1038/srep07961

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PACT/RAX regulates the migration of cerebellar granule neurons in the developing cerebellum

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Open access

Peer reviewed

PACT/RAX regulates the migration of cerebellar granule neurons in the developing cerebellum

Yue Yong, Ya Meng, Hanqing Ding, Zhiqin Fan, Yifen Tang, Chenghua Zhou, Jia Luo and Zun-Ji Ke

Scientific reports, Vol.5(1), pp.7961-7961

01/22/2015

DOI: 10.1038/srep07961

PMCID: PMC4302322

PMID: 25609658

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Abstract

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.

Amino Acid Motifs

Animals

Carrier Proteins - metabolism

Cell Differentiation

Cell Movement

Cell Proliferation

Cerebellum - growth & development

Cytoplasmic Granules - metabolism

eIF-2 Kinase - metabolism

Eye Proteins - chemistry

Eye Proteins - metabolism

Focal Adhesion Protein-Tyrosine Kinases - metabolism

Gene Knockdown Techniques

Homeodomain Proteins - chemistry

Homeodomain Proteins - metabolism

Mice, Inbred C57BL

Neuroglia - cytology

Neuroglia - metabolism

Neurons - cytology

Neurons - metabolism

Phosphorylation

Protein Binding

Transcription Factors - chemistry

Transcription Factors - metabolism

Details

Title: Subtitle: PACT/RAX regulates the migration of cerebellar granule neurons in the developing cerebellum
Creators: Yue Yong - Chinese Academy of Sciences
Ya Meng - Chinese Academy of Sciences
Hanqing Ding - Shanghai University
Zhiqin Fan - Chinese Academy of Sciences
Yifen Tang - Chinese Academy of Sciences
Chenghua Zhou - Chinese Academy of Sciences
Jia Luo - University of Kentucky
Zun-Ji Ke - Shanghai University of Traditional Chinese Medicine
Resource Type: Journal article
Publication Details: Scientific reports, Vol.5(1), pp.7961-7961
DOI: 10.1038/srep07961
PMID: 25609658
PMCID: PMC4302322
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Grant note: R01 AA015407 / NIAAA NIH HHS
Language: English
Date published: 01/22/2015
Academic Unit: Pathology
Record Identifier: 9984201255402771

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