A Calcium-Regulated MEF2 Sumoylation Switch Controls Postsynaptic Differentiation

TLDR

Postsynaptic differentiation of dendrites is an essential step in synapse formation. Activity‑dependent calcium signaling triggers calcineurin‑mediated dephosphorylation of MEF2A at serine‑408, switching its lysine‑403 modification from sumoylation to acetylation and thereby inhibiting dendritic claw differentiation. MEF2A is required for morphogenesis of cerebellar granule neuron dendritic claws, with a sumoylated repressor form promoting differentiation, and this switch may modulate activity‑dependent synapse development and plasticity.

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.