Publication Date:
2006-02-18
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Flavell, Steven W -- Cowan, Christopher W -- Kim, Tae-Kyung -- Greer, Paul L -- Lin, Yingxi -- Paradis, Suzanne -- Griffith, Eric C -- Hu, Linda S -- Chen, Chinfei -- Greenberg, Michael E -- AG05870/AG/NIA NIH HHS/ -- HD18655/HD/NICHD NIH HHS/ -- NS28829/NS/NINDS NIH HHS/ -- R01 EY013613/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 2006 Feb 17;311(5763):1008-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neurobiology Program, Children's Hospital, and Departments of Neurology and Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16484497" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Calcineurin/metabolism
;
Calcium/metabolism
;
Cells, Cultured
;
Cytoskeletal Proteins/genetics
;
Dendrites/physiology/ultrastructure
;
Excitatory Postsynaptic Potentials
;
GTPase-Activating Proteins/genetics
;
Gene Expression Regulation
;
Glutamic Acid/metabolism
;
Hippocampus/cytology/*physiology
;
MEF2 Transcription Factors
;
Mutation
;
Myogenic Regulatory Factors/genetics/*physiology
;
Nerve Tissue Proteins/genetics
;
Neurons/*physiology
;
Oligonucleotide Array Sequence Analysis
;
Phosphorylation
;
RNA Interference
;
Rats
;
Rats, Long-Evans
;
Recombinant Fusion Proteins/metabolism
;
Synapses/*physiology
;
Synaptic Transmission
;
Transcription, Genetic
;
Transfection
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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