RT Journal Article
SR Electronic
T1 Sumoylated MEF2A Coordinately Eliminates Orphan Presynaptic Sites and Promotes Maturation of Presynaptic Boutons
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 4726
OP 4740
DO 10.1523/JNEUROSCI.4191-12.2013
VO 33
IS 11
A1 Tomoko Yamada
A1 Yue Yang
A1 Ju Huang
A1 Giovanni Coppola
A1 Daniel H. Geschwind
A1 Azad Bonni
YR 2013
UL http://www.jneurosci.org/content/33/11/4726.abstract
AB Presynaptic differentiation of axons plays a fundamental role in the establishment of neuronal connectivity. However, the mechanisms that govern presynaptic differentiation in the brain remain largely to be elucidated. We report that knockdown of the transcription factor MEF2A in primary neurons and importantly in the rat cerebellar cortex in vivo robustly increases the density of orphan presynaptic sites. Remarkably, the sumoylated transcriptional repressor form of MEF2A drives the suppression of orphan presynaptic sites. We also identify the gene encoding synaptotagmin 1 (Syt1), which acts locally at presynaptic sites, as a direct repressed target gene of sumoylated MEF2A in neurons, and demonstrate that repression of Syt1 mediates MEF2A-dependent elimination of orphan presynaptic sites. Finally, we uncover a role for the MEF2A-induced elimination of orphan presynaptic sites in the accumulation of presynaptic material at large maturing presynaptic boutons. Collectively, these findings define sumoylated MEF2A and Syt1 as components of a novel cell-intrinsic mechanism that orchestrates presynaptic differentiation in the mammalian brain. Our study has important implications for understanding neuronal connectivity in brain development and disease.