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

Authors

  • Macarena S. Arrázola,

    1. Centro Basal de Excelencia para el Envejecimiento y Regeneración (CARE), Centro de Regulación Celular y Patología “Joaquín V. Luco” (CRCP) and MIFAB, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
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  • Lorena Varela-Nallar,

    1. Centro Basal de Excelencia para el Envejecimiento y Regeneración (CARE), Centro de Regulación Celular y Patología “Joaquín V. Luco” (CRCP) and MIFAB, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
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  • Marcela Colombres,

    1. Centro Basal de Excelencia para el Envejecimiento y Regeneración (CARE), Centro de Regulación Celular y Patología “Joaquín V. Luco” (CRCP) and MIFAB, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
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  • Enrique M. Toledo,

    1. Centro Basal de Excelencia para el Envejecimiento y Regeneración (CARE), Centro de Regulación Celular y Patología “Joaquín V. Luco” (CRCP) and MIFAB, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
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  • Fernando Cruzat,

    1. Laboratorio de Biología Celular y Molecular, Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile
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  • Leonardo Pavez,

    1. Laboratorio de Bioinformática y Expresión Génica, INTA-Universidad de Chile, Millennium Nucleus Center for Genomics of the Cell (CGC), Santiago, Chile
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  • Rodrigo Assar,

    1. LBMG-Centro de Modelamiento Matemático (CMM), Facultad de Ciencias Físicas y Matemáticas, Universidad de Chile, Santiago, Chile
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  • Andrés Aravena,

    1. LBMG-Centro de Modelamiento Matemático (CMM), Facultad de Ciencias Físicas y Matemáticas, Universidad de Chile, Santiago, Chile
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  • Mauricio González,

    1. Laboratorio de Bioinformática y Expresión Génica, INTA-Universidad de Chile, Millennium Nucleus Center for Genomics of the Cell (CGC), Santiago, Chile
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  • Martín Montecino,

    1. Laboratorio de Biología Celular y Molecular, Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile
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  • Alejandro Maass,

    1. LBMG-Centro de Modelamiento Matemático (CMM), Facultad de Ciencias Físicas y Matemáticas, Universidad de Chile, Santiago, Chile
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  • Servet Martínez,

    1. LBMG-Centro de Modelamiento Matemático (CMM), Facultad de Ciencias Físicas y Matemáticas, Universidad de Chile, Santiago, Chile
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  • Nibaldo C. Inestrosa

    Corresponding author
    1. Centro Basal de Excelencia para el Envejecimiento y Regeneración (CARE), Centro de Regulación Celular y Patología “Joaquín V. Luco” (CRCP) and MIFAB, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
    • CARE Biomedical Center, Faculty of Biological Sciences, Catholic University of Chile, Alameda 340 Santiago, Chile.
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  • Macarena S. Arrázola and Lorena Varela-Nallar contributed equally to this work.

Abstract

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 β-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. J. Cell. Physiol. 221: 658–667, 2009. © 2009 Wiley-Liss, Inc.

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