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Cell Mol Life Sci. 2018 Jan;75(1):67-79. doi: 10.1007/s00018-017-2634-6. Epub 2017 Sep 1.

Transcriptional regulation of CRMP5 controls neurite outgrowth through Sox5.

Author information

1
Institut NeuroMyoGène, UMR, CNRS 5310, INSERM U1217, 69000, Lyon, France.
2
Université de Lyon, Université Claude Bernard Lyon 1, 69100, Villeurbanne, France.
3
Centre de Recherche en Neurosciences de Lyon, UMR, CNRS 5292, INSERM U1028, CNRS, UMR5292, 69000, Lyon, France.
4
Laboratoire de Biométrie et Biologie Evolutive, CNRS, UMR 5558, 69100, Villeurbanne, France.
5
Service de Biostatistique, Hospices Civils de Lyon, 69003, Lyon, France.
6
Service de Neuro-Oncologie, Hospices Civils de Lyon, 69003, Lyon, France.
7
Institut NeuroMyoGène, UMR, CNRS 5310, INSERM U1217, 69000, Lyon, France. roger.besancon@univ-lyon1.fr.
8
Université de Lyon, Université Claude Bernard Lyon 1, 69100, Villeurbanne, France. roger.besancon@univ-lyon1.fr.
9
Faculté de Médecine RTH Laënnec, Institut NeuroMyoGène, Synatac Team, UMR, CNRS 5310, INSERM U1217, 69008, Lyon, France. roger.besancon@univ-lyon1.fr.

Abstract

Transcriptional regulation of proteins involved in neuronal polarity is a key process that underlies the ability of neurons to transfer information in the central nervous system. The Collapsin Response Mediator Protein (CRMP) family is best known for its role in neurite outgrowth regulation conducting to neuronal polarity and axonal guidance, including CRMP5 that drives dendrite differentiation. Although CRMP5 is able to control dendritic development, the regulation of its expression remains poorly understood. Here we identify a Sox5 consensus binding sequence in the putative promoter sequence upstream of the CRMP5 gene. By luciferase assays we show that Sox5 increases CRMP5 promoter activity, but not if the putative Sox5 binding site is mutated. We demonstrate that Sox5 can physically bind to the CRMP5 promoter DNA in gel mobility shift and chromatin immunoprecipitation assays. Using a combination of real-time RT-PCR and quantitative immunocytochemistry, we provide further evidence for a Sox5-dependent upregulation of CRMP5 transcription and protein expression in N1E115 cells: a commonly used cell line model for neuronal differentiation. Furthermore, we report that increasing Sox5 levels in this neuronal cell line inhibits neurite outgrowth. This inhibition requires CRMP5 because CRMP5 knockdown prevents the Sox5-dependent effect. We confirm the physiological relevance of the Sox5-CRMP5 pathway in the regulation of neurite outgrowth using mouse primary hippocampal neurons. These findings identify Sox5 as a critical modulator of neurite outgrowth through the selective activation of CRMP5 expression.

KEYWORDS:

CRMP5; Neurite outgrowth; Sox5; Transcriptional activation

PMID:
28864883
DOI:
10.1007/s00018-017-2634-6
[Indexed for MEDLINE]

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