Calcium/calmodulin-dependent protein kinase type IV Is a target gene of the Wnt/β-catenin signaling pathway

Macarena S. Arrázola, Lorena Varela-Nallar, Marcela Colombres, Enrique M. Toledo, Fernando Cruzat, Leonardo Pavez, Rodrigo Assar, Andrés Aravena, Mauricio González, Martín Montecino, Alejandro Maass, Servet Martínez, Nibaldo C. Inestrosa

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

58 Citas (Scopus)

Resumen

Calcium/calmodulin-dependent protein kinase IV (CaMKIV) plays a key role in the regulation of calcium-dependent gene expression. The expression of CaMKIV and the activation of CREB regulated genes are involved in memory and neuronal survival. We report here that: (a) a bioinformatic analysis of 15,476 promoters of the human genome predicted several Wnt target genes, being CaMKIV a very interesting candidate; (b) CaMKIV promoter contains TCF/LEF transcription motifs similar to those present in Wnt target genes; (c) biochemical studies indicate that lithium and the canonical ligand Wnt-3a induce CaMKIV mRNA and protein expression levels in rat hippocampal neurons as well as CaMKIV promoter activity; (d) treatment of hippocampal neurons with Wnt-3a increases the binding of b-catenin to the CaMKIV promoter: (e) In vivo activation of the Wnt signaling improve spatial memory impairment and restores the expression of CaMKIV in a mice double transgenic model for Alzheimer's disease which shows decreased levels of the kinase. We conclude that CaMKIV is regulated by the Wnt signaling pathway and that its expression could play a role in the neuroprotective function of the Wnt signaling against the Alzheimer's amyloid peptide.

Idioma originalInglés
Páginas (desde-hasta)658-667
Número de páginas10
PublicaciónJournal of Cellular Physiology
Volumen221
N.º3
DOI
EstadoPublicada - dic 2009

Áreas temáticas de ASJC Scopus

  • Fisiología
  • Bioquímica clínica
  • Biología celular

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