Editors' ChoiceNeurobiology

Transcriptional Regulation of Synaptic Change

Science's STKE  21 Feb 2006:
Vol. 2006, Issue 323, pp. tw71
DOI: 10.1126/stke.3232006tw71

Changes in synaptic activity of neurons can result in stable changes in neuronal function. Many such long-term changes are thought to be mediated by altered transcription of key target genes. Two studies have identified a role for the transcriptional regulator MEF2 in the control of synapse number (see the Perspective by Beg and Scheiffele). In cultured rat embryonic neurons, Flavell et al. found that the calcium-dependent signaling that accompanied neuronal activity led to activation of myocyte enhancer factor 2 (MEF2) and decreased numbers of synapses. Depletion of MEF2A and MEF2D caused increased synapse formation, and MEF2 activated transcription of genes known to reduce synapse formation. Shalizi et al. also found regulation of synapse number by MEF2 in rat cerebellum and cerebellar slices. MEF2A appeared to act by repressing transcription of the gene encoding the transcription factor Nur77. MEF2A showed this repression activity when sumoylated (modified by covalent linking of small ubiquitin-related modifier protein, or SUMO). Sumoylation was, in turn, dependent on calcium-dependent dephosphorylation of MEF2A. Phosphorylation of MEF2A appeared to switch MEF2A between an acetylated and a sumoylated state.

A. A. Beg, P. Scheiffele, SUMO wrestles the synapse. Science 311, 962-963 (2006). [Summary] [Full Text]

S. W. Flavell, C. W. Cowan, T.-K. Kim, P. L. Greer, Y. Lin, S. Paradis, E. C. Griffith, L. S. Hu, C. Chen, M. E. Greenberg, Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science 311, 1008-1012 (2006). [Abstract] [Full Text]

A. Shalizi, B. Gaudillière, Z. Yuan, J. Stegmüller, T. Shirogane, Q. Ge, Y. Tan, B. Schulman, J. W. Harper, A. Bonni, A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation. Science 311, 1012-1017 (2006). [Abstract] [Full Text]