Intracellular calcium and calmodulin link brain-derived neurotrophic factor to p70S6 kinase phosphorylation and dendritic protein synthesis
dc.contributor.author | Zhou, Xianju | en_US |
dc.contributor.author | Lin, David S. | en_US |
dc.contributor.author | Zheng, Fei | en_US |
dc.contributor.author | Sutton, Michael A. | en_US |
dc.contributor.author | Wang, Hongbing | en_US |
dc.date.accessioned | 2010-04-14T20:04:40Z | |
dc.date.available | 2011-03-01T16:26:47Z | en_US |
dc.date.issued | 2010-05-15 | en_US |
dc.identifier.citation | Zhou, Xianju; Lin, David S.; Zheng, Fei; Sutton, Michael A.; Wang, Hongbing (2010). "Intracellular calcium and calmodulin link brain-derived neurotrophic factor to p70S6 kinase phosphorylation and dendritic protein synthesis." Journal of Neuroscience Research 88(7): 1420-1432. <http://hdl.handle.net/2027.42/69196> | en_US |
dc.identifier.issn | 0360-4012 | en_US |
dc.identifier.issn | 1097-4547 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/69196 | |
dc.description.abstract | The mammalian target of rapamycin (mTOR)/p70S6 kinase (S6K) pathway plays an important role in brain-derived neurotrophic factor (BDNF)-mediated protein synthesis and neuroplasticity. Although many aspects of neuronal function are regulated by intracellular calcium ([Ca 2+ ] i ) and calmodulin (CaM), their functions in BDNF-induced phosphorylation of p70S6K and protein synthesis are largely unknown. Here, we report that BDNF, via TrkB-dependent activation of mTOR, induces sustained phosphorylation of p70S6K at Thr389 and Thr421/Ser424. BDNF-induced phosphorylation at Thr389 was dependent on PI3 kinase but independent of ERK-MAPK. The previously identified MAPK phosphorylation site at Thr421/Ser424 required both PI3K and MAPK in BDNF-stimulated neurons. Furthermore, we found that the reduction in [Ca 2+ ] i , but not extracellular calcium, blocked the BDNF-induced phosphorylation of p70S6K at both sites. Inhibition of CaM by W13 also blocked p70S6K phosphorylation. In correlation, W13 inhibited BDNF-induced local dendritic protein synthesis. Interestingly, sustained elevation of [Ca 2+ ] i by membrane depolarization antagonized the BDNF-induced p70S6K phosphorylation. Finally, the BDNF-induced p70S6K phosphorylation did not require the increase of calcium level through either extracellular influx or PLC-mediated intracellular calcium release. Collectively, these results indicate that the basal level of intracellular calcium gates BDNF-induced activation of p70S6K and protein synthesis through CaM. © 2009 Wiley-Liss, Inc. | en_US |
dc.format.extent | 1454867 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Neuroscience, Neurology and Psychiatry | en_US |
dc.title | Intracellular calcium and calmodulin link brain-derived neurotrophic factor to p70S6 kinase phosphorylation and dendritic protein synthesis | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Molecular, Cellular and Developmental Biology | en_US |
dc.subject.hlbsecondlevel | Neurosciences | en_US |
dc.subject.hlbsecondlevel | Psychology | en_US |
dc.subject.hlbsecondlevel | Public Health | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.subject.hlbtoplevel | Social Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Molecular and Behavioral Neuroscience Institute and Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Molecular and Behavioral Neuroscience Institute and Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan ; Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationother | Department of Physiology, Michigan State University, East Lansing, Michigan | en_US |
dc.contributor.affiliationother | Department of Physiology, Michigan State University, East Lansing, Michigan ; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan | en_US |
dc.contributor.affiliationother | Department of Physiology, Michigan State University, East Lansing, Michigan ; Neuroscience Program, Michigan State University, East Lansing, Michigan ; Cell and Molecular Biology Program, Michigan State University, East Lansing, Michigan ; Department of Physiology, 2201 BPS Building, Michigan State University, East Lansing, MI 48824 | en_US |
dc.identifier.pmid | 20029971 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/69196/1/22321_ftp.pdf | |
dc.identifier.doi | 10.1002/jnr.22321 | en_US |
dc.identifier.source | Journal of Neuroscience Research | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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