Bone morphogenetic protein-6 promotes cerebellar granule neurons survival by activation of the MEK/ERK/CREB pathway
Author
Barneda-Zahonero, Bruna
Miñano Molina, Alfredo Jesús
Badiola, Nahuai
Fadó Andrés, Rut
Xifró Collsamata, Xavier
Saura, Carlos A.
Rodríguez Álvarez, José
Publication date
2009-12-15ISSN
1059-1524
Abstract
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.
Document Type
Article
Document version
Accepted version
Language
English
Subject (CDU)
616.8 - Neurology. Neuropathology. Nervous system
Keywords
BMP
protein
proteina
Cerebellar
cerebral
Pages
13
Publisher
Molecular biology of the cell
Citation
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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- Ciències de la Salut [740]
Rights
https://creativecommons.org/licenses/by/4.0/
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-nd/4.0/