Regulation and function of stimulus-induced phosphorylation of MeCP2

doi:10.1007/s11515-014-1330-2

Front. Biol.

2014, Vol. 9

Issue (5) : 367-375 https://doi.org/10.1007/s11515-014-1330-2

REVIEW

Regulation and function of stimulus-induced phosphorylation of MeCP2

Hongda LI^1,²,Qiang CHANG^1,^2,^3,^*(

)

1. Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA
2. Genetics Training Program, University of Wisconsin-Madison, Madison, Wisconsin 53705,USA
3. Department of Neurology, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA

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Abstract

DNA methylation-dependent epigenetic regulation plays important roles in the development and function of the mammalian nervous system. MeCP2 is a key player in recognizing methylated DNA and interpreting the epigenetic information encoded in different DNA methylation patterns. Mutations in the MECP2 gene cause Rett syndrome, a devastating neurological disease that shares many features with autism. One interesting aspect of MeCP2 function is that it can be phosphorylated in response to diverse stimuli. Insights into the regulation and function of MeCP2 phosphorylation will help improve our understanding of how MeCP2 integrates environmental stimuli in neuronal nuclei to generate adaptive responses and may eventually lead to treatments for patients.

Keywords MeCP2 phosphorylation Rett syndrome

Corresponding Author(s): Qiang CHANG

Just Accepted Date: 13 August 2014 Online First Date: 22 September 2014 Issue Date: 11 October 2014

Cite this article:

Hongda LI,Qiang CHANG. Regulation and function of stimulus-induced phosphorylation of MeCP2[J]. Front. Biol., 2014, 9(5): 367-375.

URL:

https://academic.hep.com.cn/fib/EN/10.1007/s11515-014-1330-2
https://academic.hep.com.cn/fib/EN/Y2014/V9/I5/367

Fig.1 Distribution of known phosphorylation sites on the MeCP2 protein. Neuronal activity-induced phosphorylation sites are marked in red. MBD, methyl-CpG binding domain; TRD, transcriptional repression domain.

Fig.2 Neuronal activity-induced phosphorylation and dephosphorylation modify MeCP2 function. Stimulation of NMDA receptors, DA receptors and 5-HT receptors, as well as membrane depolarization, activates L-type calcium channels on the cellular membrane and induces calcium influx. Specific kinases and phosphatases in the nucleus are subsequently activated and modify the phosphorylation status of MeCP2. Phosphoprylation of S421, together with dephosphorylation of S80, may modulate the binding of MeCP2 to the promoters of specific genes. Dephosphorylation of S80 releases DGCR8 from MeCP2 to regulate microRNA processing. Phosphorylation of T308 interrupts the association between MeCP2 and NCoR co-repressor complex. NMDA receptors, N-methyl-D-aspartate receptors; DA receptors, Dopamine receptors; 5-HT receptors, 5-hydroxytryptamine receptors or serotonin receptors.

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