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Cited by 1,561Nerve injury and regenerationNeuroscience and Neuropharmacology ResearchNuclear Receptors and Signaling

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Ca2+ Influx Regulates BDNF Transcription by a CREB Family Transcription Factor-Dependent Mechanism

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Tao, Xu, Finkbeiner, Steven, Arnold, Donald B., Shaywitz, Adam J., Greenberg, Michael E.·1998·Neuron
DOI 10.1016/s0896-6273(00)81010-7
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Abstract

CREB is a transcription factor implicated in the control of adaptive neuronal responses. Although one function of CREB in neurons is believed to be the regulation of genes whose products control synaptic function, the targets of CREB that mediate synaptic function have not yet been identified. This report describes experiments demonstrating that CREB or a closely related protein mediates Ca2+-dependent regulation of BDNF, a neurotrophin that modulates synaptic activity. In cortical neurons, Ca2+ influx triggers phosphorylation of CREB, which by binding to a critical Ca2+ response element (CRE) within the BDNF gene activates BDNF transcription. Mutation of the BDNF CRE or an adjacent novel regulatory element as well as a blockade of CREB function resulted in a dramatic loss of BDNF transcription. These findings suggest that a CREB family member acts cooperatively with an additional transcription factor(s) to regulate BDNF transcription. We conclude that the BDNF gene is a CREB family target whose protein product functions at synapses to control adaptive neuronal responses.

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Metadata

Authors
Tao, X., Finkbeiner, S., Arnold, D. B., Shaywitz, A. J., & Greenberg, M. E.
Affiliations
  • Harvard University (US)
  • Boston Children's Hospital (US)
Corresponding author
Greenberg, Michael E.
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
1998-04
Volume
20
Issue
4
Pages
709-726
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/s0896-6273(00)81010-7
OpenAlex
W1992529363
Cited by
1,561
References
7
Citations by year
2026: 36 · 2025: 41 · 2024: 36 · 2023: 51 · 2022: 42 · 2021: 49 · 2020: 58 · 2019: 48 · 2018: 57 · 2017: 72 · 2016: 69 · 2015: 61 · 2014: 59 · 2013: 66 · 2012: 63
FWCI
23.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5k08ns001817-02)
  • National Institute of Neurological Disorders and Stroke (K08 NS01817, NS288829)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655, P30HD-18655)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Keywords
brain-derived neurotrophic factor, CREB, calcium influx, transcriptional regulation, CREB phosphorylation, cortical neurons, synaptic plasticity, neurotrophins, transcription factor cooperativity
MeSH terms
Animals, Base Sequence, Calcium, Cells, Cultured, Cerebral Cortex, Embryo, Mammalian, Exons, Gene Expression Regulation, Kinetics, Neurons, Phosphorylation, Recombinant Fusion Proteins, Regulatory Sequences, Nucleic Acid, Synapses, Transcription Factors, Transcription, Genetic, Transfection, Calcium Channels, Signal Transduction, Polymerase Chain Reaction, Mutagenesis, Site-Directed, Cyclic AMP Response Element-Binding Protein, DNA Primers, Brain-Derived Neurotrophic Factor, Biolistics, Calcium Channels, L-Type, Rats

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