When MeCP2 gets phosphorylated

Mutations in MeCP2, a methyl-CpG-binding protein that functions as a regulator of gene expression, are the major cause of Rett Syndrome (RTT), an X-linked progressive autism spectrum disorder. Recent biochemical analysis has identified 8 phosphorylation sites on the MeCP2 protein. Among these, serine 80 (S80) is phosphorylated in resting neurons but dephosphorylated in active neurons, whereas serine 421 (S421) is dephosphorylated in resting neurons but phosphorylated in active neurons. We have generated several Mecp2 knockin alleles carrying point mutations that either abolish or mimic phosphorylation at S80 and S421 on the MeCP2 protein. We hope to use activity-dependent MeCP2 phosphoryalation as a model to better understand the mechanism by which mammalian brains integrate environmental stimuli, convert the information to cellular “memory” and make behavioral response.