Bone morphogenetic protein-6 promotes cerebellar granule neurons survival by activation of the MEK/ERK/CREB pathway
Autor/a
Barneda-Zahonero, Bruna
Miñano Molina, Alfredo Jesús
Badiola, Nahuai
Fadó Andrés, Rut
Xifró Collsamata, Xavier
Saura, Carlos A.
Rodríguez Álvarez, José
Fecha de publicación
2009-12-15ISSN
1059-1524
Resumen
Bone morphogenetic proteins (BMPs) have been implicated in the generation and postnatal differentiation of cerebellar granule cells (CGCs). Here, we examined the eventual role of BMPs on the survival of these neurons. Lack of depolarization causes CGC death by apoptosis in vivo, a phenomenon that is mimicked in vitro by deprivation of high potassium in cultured CGCs. We have found that BMP-6, but not BMP-7, is able to block low potassium–mediated apoptosis in CGCs. The neuroprotective effect of BMP-6 is not accompanied by an increase of Smad translocation to the nucleus, suggesting that the canonical pathway is not involved. By contrast, activation of the MEK/ERK/CREB pathway by BMP-6 is necessary for its neuroprotective effect, which involves inhibition of caspase activity and an increase in Bcl-2 protein levels. Other pathways involved in the regulation of CGC survival, such as the c-Jun terminal kinase and the phosphatidylinositol 3-kinase (PI3K)-Akt/PKB, were not affected by BMP-6. Moreover, failure of BMP-7 to activate the MEK/ERK/CREB pathway could explain its inability to protect CGCs from low potassium–mediated apoptosis. Thus, this study demonstrates that BMP-6 acting through the noncanonical MEK/ERK/CREB pathway plays a crucial role on CGC survival.
Tipo de documento
Artículo
Versión del documento
Versión aceptada
Lengua
English
Materias (CDU)
616.8 - Neurología. Neuropatología. Sistema nervioso
Palabras clave
BMP
protein
proteina
Cerebellar
cerebral
Páginas
13
Publicado por
Molecular biology of the cell
Citación
Barneda-Zahonero, B., Miñano-Molina, A., Badiola, N., Fadó, R., Xifró, X., Saura, C. A., & Rodríguez-Alvarez, J. (2009). «Bone morphogenetic protein-6 promotes cerebellar granule neurons survival by activation of the MEK/ERK/CREB pathway». Molecular biology of the cell, 20(24), 5051-5063
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https://creativecommons.org/licenses/by/4.0/
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