Functional whole-genome analysis identifies polo-like kinase 2 and poliovirus receptor as essential for neuronal differentiation upstream of the negative regulator αB-crystallin

Cristina Draghetti, Catherine Salvat, Francisca Zanoguera, Marie Laure Curchod, Chloé Vignaud, Helene Peixoto, Alessandro Di Cara, David Fischer, Mohanraj Dhanabal, Goutopoulos Andreas, Hadi Abderrahim, Christian Rommel, Montserrat Camps

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

This study aimed at identifying transcriptional changes associated to neuronal differentiation induced by six distinct stimuli using whole-genome microarray hybridization analysis. Bioinformatics analyses revealed the clustering of these six stimuli into two categories, suggesting separate gene/pathway dependence. Treatment with specific inhibitors demonstrated the requirement of both Janus kinase and microtubule-associated protein kinase activation to trigger differentiation with nerve growth factor (NGF) and dibutyryl cAMP. Conversely, activation of protein kinase A, phosphatidylinositol-3-kinase α, and mammalian target of rapamycin, although required for dibutyryl cAMP-induced differentiation, exerted a negative feedback on NGF-induced differentiation. We identified Polo-like kinase 2 (Plk2) and poliovirus receptor (PVR) as indispensable for NGF-driven neuronal differentiation αB-crystallin (Cryab) as an inhibitor of this process. Silencing of Plk2 or PVR blocked NGF-triggered differentiation and Cryab down-regulation, while silencing of Cryab enhanced NGF-induced differentiation. Our results position both Plk2 and PVR upstream of the negative regulator Cryab in the pathway(s) leading to neuronal differentiation triggered by NGF.

Original languageEnglish
Pages (from-to)32053-32065
Number of pages13
JournalJournal of Biological Chemistry
Volume284
Issue number46
DOIs
Publication statusPublished - 30 Nov 2009
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Draghetti, C., Salvat, C., Zanoguera, F., Curchod, M. L., Vignaud, C., Peixoto, H., Di Cara, A., Fischer, D., Dhanabal, M., Andreas, G., Abderrahim, H., Rommel, C., & Camps, M. (2009). Functional whole-genome analysis identifies polo-like kinase 2 and poliovirus receptor as essential for neuronal differentiation upstream of the negative regulator αB-crystallin. Journal of Biological Chemistry, 284(46), 32053-32065. https://doi.org/10.1074/jbc.M109.009324