Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 17 February 2006:
Vol. 311. no. 5763, pp. 1008 - 1012
DOI: 10.1126/science.1122511
Prev | Table of Contents | Next

Reports

Activity-Dependent Regulation of MEF2 Transcription Factors Suppresses Excitatory Synapse Number

Steven W. Flavell,1,2* Christopher W. Cowan,1*{dagger} Tae-Kyung Kim,1 Paul L. Greer,1 Yingxi Lin,1 Suzanne Paradis,1 Eric C. Griffith,1 Linda S. Hu,1 Chinfei Chen,1 Michael E. Greenberg1{ddagger}

In the mammalian nervous system, neuronal activity regulates the strength and number of synapses formed. The genetic program that coordinates this process is poorly understood. We show that myocyte enhancer factor 2 (MEF2) transcription factors suppressed excitatory synapse number in a neuronal activity- and calcineurin-dependent manner as hippocampal neurons formed synapses. In response to increased neuronal activity, calcium influx into neurons induced the activation of the calcium/calmodulin-regulated phosphatase calcineurin, which dephosphorylated and activated MEF2. When activated, MEF2 promoted the transcription of a set of genes, including arc and synGAP, that restrict synapse number. These findings define an activity-dependent transcriptional program that may control synapse number during development.

1 Neurobiology Program, Children's Hospital, and Departments of Neurology and Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
2 Program in Neuroscience, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.

* These authors contributed equally to this work.

{dagger} Present address: Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390–9070, USA.

{ddagger} To whom correspondence should be addressed. E-mail: michael.greenberg{at}childrens.harvard.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
SUMOylation of the MAGUK protein CASK regulates dendritic spinogenesis.
H.-W. Chao, C.-J. Hong, T.-N. Huang, Y.-L. Lin, and Y.-P. Hsueh (2008)
J. Cell Biol. 182, 141-155
   Abstract »    Full Text »    PDF »
Identifying Autism Loci and Genes by Tracing Recent Shared Ancestry.
E. M. Morrow, S.-Y. Yoo, S. W. Flavell, T.-K. Kim, Y. Lin, R. S. Hill, N. M. Mukaddes, S. Balkhy, G. Gascon, A. Hashmi, et al. (2008)
Science 321, 218-223
   Abstract »    Full Text »    PDF »
MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and function.
A. C. Barbosa, M.-S. Kim, M. Ertunc, M. Adachi, E. D. Nelson, J. McAnally, J. A. Richardson, E. T. Kavalali, L. M. Monteggia, R. Bassel-Duby, et al. (2008)
PNAS 105, 9391-9396
   Abstract »    Full Text »    PDF »
Transcription factor MEF2C influences neural stem/progenitor cell differentiation and maturation in vivo.
H. Li, J. C. Radford, M. J. Ragusa, K. L. Shea, S. R. McKercher, J. D. Zaremba, W. Soussou, Z. Nie, Y.-J. Kang, N. Nakanishi, et al. (2008)
PNAS 105, 9397-9402
   Abstract »    Full Text »    PDF »
Myocyte Enhancer Factor 2C as a Neurogenic and Antiapoptotic Transcription Factor in Murine Embryonic Stem Cells.
Z. Li, S. R. McKercher, J. Cui, Z. Nie, W. Soussou, A. J. Roberts, T. Sallmen, J. H. Lipton, M. Talantova, S.-i. Okamoto, et al. (2008)
J. Neurosci. 28, 6557-6568
   Abstract »    Full Text »    PDF »
The MADS transcription factor Mef2c is a pivotal modulator of myeloid cell fate.
A. Schuler, M. Schwieger, A. Engelmann, K. Weber, S. Horn, U. Muller, M. A. Arnold, E. N. Olson, and C. Stocking (2008)
Blood 111, 4532-4541
   Abstract »    Full Text »    PDF »
Myocyte Enhancer Factor 2A Is Transcriptionally Autoregulated.
B. Ramachandran, G. Yu, S. Li, B. Zhu, and T. Gulick (2008)
J. Biol. Chem. 283, 10318-10329
   Abstract »    Full Text »    PDF »
The regulation of dendritic arbor development and plasticity by glutamatergic synaptic input: a review of the synaptotrophic hypothesis.
H. Cline and K. Haas (2008)
J. Physiol. 586, 1509-1517
   Abstract »    Full Text »    PDF »
Phosphorylation-Dependent Sumoylation Regulates Estrogen-Related Receptor-{alpha} and -{gamma} Transcriptional Activity through a Synergy Control Motif.
A. M. Tremblay, B. J. Wilson, X.-J. Yang, and V. Giguere (2008)
Mol. Endocrinol. 22, 570-584
   Abstract »    Full Text »    PDF »
mef2 activity levels differentially affect gene expression during Drosophila muscle development.
S. J. Elgar, J. Han, and M. V. Taylor (2008)
PNAS 105, 918-923
   Abstract »    Full Text »    PDF »
MEF2: a central regulator of diverse developmental programs.
M. J. Potthoff and E. N. Olson (2007)
Development 134, 4131-4140
   Abstract »    Full Text »    PDF »
Nemo-Like Kinase-Myocyte Enhancer Factor 2A Signaling Regulates Anterior Formation in Xenopus Development.
K. Satoh, J. Ohnishi, A. Sato, M. Takeyama, S.-i. Iemura, T. Natsume, and H. Shibuya (2007)
Mol. Cell. Biol. 27, 7623-7630
   Abstract »    Full Text »    PDF »
PIASx Is a MEF2 SUMO E3 Ligase That Promotes Postsynaptic Dendritic Morphogenesis.
A. Shalizi, P. M. Bilimoria, J. Stegmuller, B. Gaudilliere, Y. Yang, K. Shuai, and A. Bonni (2007)
J. Neurosci. 27, 10037-10046
   Abstract »    Full Text »    PDF »
Quantitative expression profiling of identified neurons reveals cell-specific constraints on highly variable levels of gene expression.
D. J. Schulz, J.-M. Goaillard, and E. E. Marder (2007)
PNAS 104, 13187-13191
   Abstract »    Full Text »    PDF »
Cabin1 Represses MEF2 Transcriptional Activity by Association with a Methyltransferase, SUV39H1.
H. Jang, D.-E. Choi, H. Kim, E.-J. Cho, and H.-D. Youn (2007)
J. Biol. Chem. 282, 11172-11179
   Abstract »    Full Text »    PDF »
Network activity-independent coordinated gene expression program for synapse assembly.
L. M. Valor, P. Charlesworth, L. Humphreys, C. N. G. Anderson, and S. G. N. Grant (2007)
PNAS 104, 4658-4663
   Abstract »    Full Text »    PDF »
AKT and CDK5/p35 Mediate Brain-derived Neurotrophic Factor Induction of DARPP-32 in Medium Size Spiny Neurons in Vitro.
A. Bogush, S. Pedrini, J. Pelta-Heller, T. Chan, Q. Yang, Z. Mao, E. Sluzas, T. Gieringer, and M. E. Ehrlich (2007)
J. Biol. Chem. 282, 7352-7359
   Abstract »    Full Text »    PDF »
Histone Deacetylase 3 Interacts with and Deacetylates Myocyte Enhancer Factor 2.
S. Gregoire, L. Xiao, J. Nie, X. Zhang, M. Xu, J. Li, J. Wong, E. Seto, and X.-J. Yang (2007)
Mol. Cell. Biol. 27, 1280-1295
   Abstract »    Full Text »    PDF »
Differential Effects of Ca2+ and cAMP on Transcription Mediated by MEF2D and cAMP-response Element-binding Protein in Hippocampal Neurons.
J. L. Belfield, C. Whittaker, M. Z. Cader, and S. Chawla (2006)
J. Biol. Chem. 281, 27724-27732
   Abstract »    Full Text »    PDF »
MEF2 Activates a Genetic Program Promoting Chamber Dilation and Contractile Dysfunction in Calcineurin-Induced Heart Failure.
R. J. van Oort, E. van Rooij, M. Bourajjaj, J. Schimmel, M. A. Jansen, R. van der Nagel, P. A. Doevendans, M. D. Schneider, C. J.A. van Echteld, and L. J. De Windt (2006)
Circulation 114, 298-308
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)