A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation

Aryaman Shalizi; Brice Gaudillière; Zengqiang Yuan; Judith Stegmüller; Takahiro Shirogane; Qingyuan Ge; Yi Tan; Brenda Schulman; J. Wade Harper; Azad Bonni

doi:10.1126/science.1122513

A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation

Aryaman Shalizi
, Brice Gaudillière
, Zengqiang Yuan
, Judith Stegmüller
, Takahiro Shirogane
, Qingyuan Ge
, Yi Tan
, Brenda Schulman
, J. Wade Harper
, Azad Bonni

Department of Neuroscience

Research output: Contribution to journal › Article › peer-review

405 Scopus citations

Abstract

Postsynaptic differentiation of dendrites is an essential step in synapse formation. We report here a requirement for the transcription factor myocyte enhancer factor 2A (MEF2A) in the morphogenesis of postsynaptic granule neuron dendritic claws in the cerebellar cortex. A transcriptional repressor form of MEF2A that is sumoylated at lysine-403 promoted dendritic claw differentiation. Activity-dependent calcium signaling induced a calcineurin-mediated dephosphorylation of MEF2A at serine-408 and, thereby, promoted a switch from sumoylation to acetylation at lysine-403, which led to inhibition of dendritic claw differentiation. Our findings define a mechanism underlying postsynaptic differentiation that may modulate activity-dependent synapse development and plasticity in the brain.

Original language	English
Pages (from-to)	1012-1017
Number of pages	6
Journal	Science
Volume	311
Issue number	5763
DOIs	https://doi.org/10.1126/science.1122513
State	Published - Feb 17 2006

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title = "A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation",

abstract = "Postsynaptic differentiation of dendrites is an essential step in synapse formation. We report here a requirement for the transcription factor myocyte enhancer factor 2A (MEF2A) in the morphogenesis of postsynaptic granule neuron dendritic claws in the cerebellar cortex. A transcriptional repressor form of MEF2A that is sumoylated at lysine-403 promoted dendritic claw differentiation. Activity-dependent calcium signaling induced a calcineurin-mediated dephosphorylation of MEF2A at serine-408 and, thereby, promoted a switch from sumoylation to acetylation at lysine-403, which led to inhibition of dendritic claw differentiation. Our findings define a mechanism underlying postsynaptic differentiation that may modulate activity-dependent synapse development and plasticity in the brain.",

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T1 - A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation

AU - Shalizi, Aryaman

AU - Gaudillière, Brice

AU - Yuan, Zengqiang

AU - Stegmüller, Judith

AU - Shirogane, Takahiro

AU - Ge, Qingyuan

AU - Tan, Yi

AU - Schulman, Brenda

AU - Harper, J. Wade

AU - Bonni, Azad

PY - 2006/2/17

Y1 - 2006/2/17

N2 - Postsynaptic differentiation of dendrites is an essential step in synapse formation. We report here a requirement for the transcription factor myocyte enhancer factor 2A (MEF2A) in the morphogenesis of postsynaptic granule neuron dendritic claws in the cerebellar cortex. A transcriptional repressor form of MEF2A that is sumoylated at lysine-403 promoted dendritic claw differentiation. Activity-dependent calcium signaling induced a calcineurin-mediated dephosphorylation of MEF2A at serine-408 and, thereby, promoted a switch from sumoylation to acetylation at lysine-403, which led to inhibition of dendritic claw differentiation. Our findings define a mechanism underlying postsynaptic differentiation that may modulate activity-dependent synapse development and plasticity in the brain.

AB - Postsynaptic differentiation of dendrites is an essential step in synapse formation. We report here a requirement for the transcription factor myocyte enhancer factor 2A (MEF2A) in the morphogenesis of postsynaptic granule neuron dendritic claws in the cerebellar cortex. A transcriptional repressor form of MEF2A that is sumoylated at lysine-403 promoted dendritic claw differentiation. Activity-dependent calcium signaling induced a calcineurin-mediated dephosphorylation of MEF2A at serine-408 and, thereby, promoted a switch from sumoylation to acetylation at lysine-403, which led to inhibition of dendritic claw differentiation. Our findings define a mechanism underlying postsynaptic differentiation that may modulate activity-dependent synapse development and plasticity in the brain.

UR - https://www.scopus.com/pages/publications/33144473786

U2 - 10.1126/science.1122513

DO - 10.1126/science.1122513

M3 - Article

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AN - SCOPUS:33144473786

SN - 0036-8075

VL - 311

SP - 1012

EP - 1017

JO - Science

JF - Science

IS - 5763

ER -

A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation

Abstract

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