{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T19:13:39Z","timestamp":1770750819997,"version":"3.50.0"},"reference-count":61,"publisher":"American Society for Cell Biology (ASCB)","issue":"24","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2009,12,15]]},"abstract":"<jats:p>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\u2013mediated 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\u2013mediated apoptosis. Thus, this study demonstrates that BMP-6 acting through the noncanonical MEK\/ERK\/CREB pathway plays a crucial role on CGC survival.<\/jats:p>","DOI":"10.1091\/mbc.e09-05-0424","type":"journal-article","created":{"date-parts":[[2009,10,22]],"date-time":"2009-10-22T01:45:28Z","timestamp":1256175928000},"page":"5051-5063","source":"Crossref","is-referenced-by-count":32,"title":["Bone Morphogenetic Protein-6 Promotes Cerebellar Granule Neurons Survival by Activation of the MEK\/ERK\/CREB Pathway"],"prefix":"10.1091","volume":"20","author":[{"given":"Bruna","family":"Barneda-Zahonero","sequence":"first","affiliation":[{"name":"*Institut de Neurociencies and Departament de Bioqu\u00edmica i Biolog\u00eda Molecular Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Valles, Barcelona, Spain; and"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo","family":"Mi\u00f1ano-Molina","sequence":"additional","affiliation":[{"name":"*Institut de Neurociencies and Departament de Bioqu\u00edmica i Biolog\u00eda Molecular Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Valles, Barcelona, Spain; and"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nahuai","family":"Badiola","sequence":"additional","affiliation":[{"name":"*Institut de Neurociencies and Departament de Bioqu\u00edmica i Biolog\u00eda Molecular Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Valles, Barcelona, Spain; and"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rut","family":"Fad\u00f3","sequence":"additional","affiliation":[{"name":"*Institut de Neurociencies and Departament de Bioqu\u00edmica i Biolog\u00eda Molecular Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Valles, Barcelona, Spain; and"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xavier","family":"Xifr\u00f3","sequence":"additional","affiliation":[{"name":"*Institut de Neurociencies and Departament de Bioqu\u00edmica i Biolog\u00eda Molecular Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Valles, Barcelona, Spain; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos A.","family":"Saura","sequence":"additional","affiliation":[{"name":"*Institut de Neurociencies and Departament de Bioqu\u00edmica i Biolog\u00eda Molecular Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Valles, Barcelona, Spain; and"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Rodr\u00edguez-Alvarez","sequence":"additional","affiliation":[{"name":"*Institut de Neurociencies and Departament de Bioqu\u00edmica i Biolog\u00eda Molecular Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Valles, Barcelona, Spain; and"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1076","reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/9189","volume":"2","author":"Alder J.","year":"1999","journal-title":"Nat. Neurosci"},{"key":"B2","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1523\/JNEUROSCI.23-01-00260.2003","volume":"23","author":"Angley C.","year":"2003","journal-title":"J. Neurosci"},{"key":"B3","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1523\/JNEUROSCI.17-02-00553.1997","volume":"17","author":"Armstrong R. C.","year":"1997","journal-title":"J. Neurosci"},{"key":"B4","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1046\/j.1471-4159.1994.63051880.x","volume":"63","author":"Aruga J.","year":"1994","journal-title":"J. Neurochem"},{"key":"B5","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/0165-3806(88)90139-3","volume":"468","author":"Balazs R.","year":"1988","journal-title":"Brain Res"},{"key":"B6","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/36579","volume":"390","author":"Ben Arie N.","year":"1997","journal-title":"Nature"},{"key":"B7","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1126\/science.286.5443.1358","volume":"286","author":"Bonni A.","year":"1999","journal-title":"Science"},{"key":"B8","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1046\/j.1471-4159.2002.00795.x","volume":"80","author":"Borodinsky L. N.","year":"2002","journal-title":"J. Neurochem"},{"key":"B9","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0165-0173(88)90006-9","volume":"472","author":"Burgoyne R. D.","year":"1988","journal-title":"Brain Res"},{"key":"B10","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.tins.2005.06.005","volume":"28","author":"Carlezon W. A.","year":"2005","journal-title":"Trends Neurosci"},{"key":"B11","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1161\/01.STR.0000051507.64423.00","volume":"34","author":"Chang C. F.","year":"2003","journal-title":"Stroke"},{"key":"B12","doi-asserted-by":"crossref","first-page":"4335","DOI":"10.1523\/JNEUROSCI.22-11-04335.2002","volume":"22","author":"Coffey E. T.","year":"2002","journal-title":"J. Neurosci"},{"key":"B13","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.brainres.2004.02.068","volume":"1010","author":"Cox S.","year":"2004","journal-title":"Brain Res"},{"key":"B14","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/0076-6879(87)52074-2","volume":"152","author":"Cullen B. R.","year":"1987","journal-title":"Methods Enzymol"},{"key":"B15","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1523\/JNEUROSCI.17-05-01548.1997","volume":"17","author":"D'Mello S. R.","year":"1997","journal-title":"J. Neurosci"},{"key":"B16","doi-asserted-by":"crossref","first-page":"10989","DOI":"10.1073\/pnas.90.23.10989","volume":"90","author":"D'Mello S. R.","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"B17","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0092-8674(00)80405-5","volume":"91","author":"Datta S. R.","year":"1997","journal-title":"Cell"},{"key":"B18","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1523\/JNEUROSCI.07-07-02203.1987","volume":"7","author":"Gallo V.","year":"1987","journal-title":"J. Neurosci"},{"key":"B19","doi-asserted-by":"crossref","first-page":"7880","DOI":"10.1158\/0008-5472.CAN-06-0254","volume":"66","author":"Gao L.","year":"2006","journal-title":"Cancer Res"},{"key":"B20","doi-asserted-by":"crossref","first-page":"33361","DOI":"10.1074\/jbc.M205053200","volume":"277","author":"Ghosh-Choudhury N.","year":"2002","journal-title":"J. Biol. Chem"},{"key":"B21","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1002\/jnr.10438","volume":"70","author":"Gratacos E.","year":"2002","journal-title":"J. Neurosci. Res"},{"key":"B22","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1038\/nm904","volume":"9","author":"Hallahan A. R.","year":"2003","journal-title":"Nat. Med"},{"key":"B23","doi-asserted-by":"crossref","first-page":"4624","DOI":"10.1523\/JNEUROSCI.4701-05.2006","volume":"26","author":"Han M. H.","year":"2006","journal-title":"J. Neurosci"},{"key":"B24","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1046\/j.1471-4159.2002.01219.x","volume":"83","author":"Harris C.","year":"2002","journal-title":"J. Neurochem"},{"key":"B25","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.brainres.2004.06.072","volume":"1022","author":"Harvey B. K.","year":"2004","journal-title":"Brain Res"},{"key":"B26","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1002\/(SICI)1097-4547(19990501)56:3<248::AID-JNR4>3.0.CO;2-U","volume":"56","author":"Iantosca M. R.","year":"1999","journal-title":"J. Neurosci. Res"},{"key":"B27","doi-asserted-by":"crossref","first-page":"31133","DOI":"10.1074\/jbc.M101463200","volume":"276","author":"Izumi M.","year":"2001","journal-title":"J. Biol. Chem"},{"key":"B28","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1083\/jcb.200603061","volume":"175","author":"Je H. S.","year":"2006","journal-title":"J. Cell Biol"},{"key":"B29","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nn1870","volume":"10","author":"Jia Y.","year":"2007","journal-title":"Nat. Neurosci"},{"key":"B30","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1111\/j.1460-9568.1997.tb01527.x","volume":"9","author":"Jordan J.","year":"1997","journal-title":"Eur. J. Neurosci"},{"key":"B31","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1046\/j.1460-9568.2002.02124.x","volume":"16","author":"Lafon-Cazal M.","year":"2002","journal-title":"Eur. J. Neurosci"},{"key":"B32","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1074\/jbc.M308665200","volume":"279","author":"Lemonnier J.","year":"2004","journal-title":"J. Biol. Chem"},{"key":"B33","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/S0896-6273(02)00828-0","volume":"35","author":"Lonze B. E.","year":"2002","journal-title":"Neuron"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e06-12-1110"},{"key":"B35","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1146\/annurev.biochem.67.1.753","volume":"67","author":"Massague J.","year":"1998","journal-title":"Annu. Rev. Biochem"},{"key":"B36","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S8756-3282(99)00113-1","volume":"25","author":"Miyazono K.","year":"1999","journal-title":"Bone"},{"key":"B37","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.cytogfr.2005.01.009","volume":"16","author":"Miyazono K.","year":"2005","journal-title":"Cytokine Growth Factor Rev"},{"key":"B38","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1046\/j.1460-9568.2002.02232.x","volume":"16","author":"Monti B.","year":"2002","journal-title":"Eur. J. Neurosci"},{"key":"B39","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1046\/j.1471-4159.1999.0730568.x","volume":"73","author":"Moran J.","year":"1999","journal-title":"J. Neurochem"},{"key":"B40","doi-asserted-by":"crossref","first-page":"11382","DOI":"10.1073\/pnas.93.21.11382","volume":"93","author":"Naldini L.","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"B41","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1046\/j.1471-4159.2001.00273.x","volume":"77","author":"Nonner D.","year":"2001","journal-title":"J. Neurochem"},{"key":"B42","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1111\/j.1471-4159.2006.04390.x","volume":"101","author":"Obara Y.","year":"2007","journal-title":"J. Neurochem"},{"key":"B43","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1523\/JNEUROSCI.3202-05.2006","volume":"26","author":"Qin L.","year":"2006","journal-title":"J. Neurosci"},{"key":"B44","doi-asserted-by":"crossref","first-page":"3159","DOI":"10.1242\/dev.01188","volume":"131","author":"Rios I.","year":"2004","journal-title":"Development"},{"key":"B45","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/0896-6273(94)90310-7","volume":"12","author":"Ryder E. F.","year":"1994","journal-title":"Neuron"},{"key":"B46","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.1523\/JNEUROSCI.5060-04.2005","volume":"25","author":"Subramaniam S.","year":"2005","journal-title":"J. Neurosci"},{"key":"B47","doi-asserted-by":"crossref","first-page":"8904","DOI":"10.1074\/jbc.M210037200","volume":"278","author":"Subramaniam S.","year":"2003","journal-title":"J. Biol. Chem"},{"key":"B48","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1111\/j.1460-9568.1997.tb01434.x","volume":"9","author":"Tanabe H.","year":"1997","journal-title":"Eur. J. Neurosci"},{"key":"B49","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1126\/science.8140412","volume":"264","author":"ten Dijke P.","year":"1994","journal-title":"Science"},{"key":"B50","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1161\/hs0901.095650","volume":"32","author":"Wang Y.","year":"2001","journal-title":"Stroke"},{"key":"B51","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1523\/JNEUROSCI.18-02-00751.1998","volume":"18","author":"Watson A.","year":"1998","journal-title":"J. Neurosci"},{"key":"B52","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/0896-6273(93)90074-2","volume":"11","author":"Wood K. A.","year":"1993","journal-title":"Neuron"},{"key":"B53","doi-asserted-by":"crossref","first-page":"8599","DOI":"10.1128\/MCB.01062-06","volume":"26","author":"Xiang H.","year":"2006","journal-title":"Mol. Cell Biol"},{"key":"B54","doi-asserted-by":"crossref","first-page":"6801","DOI":"10.1074\/jbc.M504571200","volume":"281","author":"Xifro X.","year":"2006","journal-title":"J. Biol. Chem"},{"key":"B55","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1111\/j.1460-9568.2005.03935.x","volume":"21","author":"Xifro X.","year":"2005","journal-title":"Eur. J. Neurosci"},{"key":"B56","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/jnr.10210","volume":"68","author":"Yabe T.","year":"2002","journal-title":"J. Neurosci. Res"},{"key":"B57","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1038\/33451","volume":"392","author":"York R. D.","year":"1998","journal-title":"Nature"},{"key":"B58","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1038\/sj.onc.1202521","volume":"18","author":"Yue J.","year":"1999","journal-title":"Oncogene"},{"key":"B59","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1002\/jnr.20024","volume":"75","author":"Zhong J.","year":"2004","journal-title":"J. Neurosci. Res"},{"key":"B60","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/jnr.20422","volume":"80","author":"Zhu D.","year":"2005","journal-title":"J. Neurosci. Res"},{"key":"B61","doi-asserted-by":"crossref","first-page":"9873","DOI":"10.1128\/JVI.72.12.9873-9880.1998","volume":"72","author":"Zufferey R.","year":"1998","journal-title":"J. Virol"}],"container-title":["Molecular Biology of the Cell"],"original-title":[],"language":"en","deposited":{"date-parts":[[2020,5,23]],"date-time":"2020-05-23T05:48:12Z","timestamp":1590212892000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.molbiolcell.org\/doi\/10.1091\/mbc.e09-05-0424"}},"subtitle":[],"editor":[{"given":"Marianne","family":"Bronner-Fraser","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2009,12,15]]},"references-count":61,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2009,12,15]]}},"alternative-id":["10.1091\/mbc.e09-05-0424"],"URL":"https:\/\/doi.org\/10.1091\/mbc.e09-05-0424","relation":{},"ISSN":["1059-1524","1939-4586"],"issn-type":[{"value":"1059-1524","type":"print"},{"value":"1939-4586","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,12,15]]}}}