Investigation of the Importance of a hitherto Uncharacterized Mecp2-Isoform for Neuronal Morphogenesis and Chromatin related functions

Reference:
Charlotte Kilstrup-Nielsen

Abstract:
MeCP2 is a protein that has been found to bind and probably regulate important aspects of chromatin but it is still not clear how defects in MeCP2 cause the neurologic problems of RTT. It has become clear that MeCP2 gets phosphorylated in neurons that are activated by external stimuli but we still need to understand in more details how and when these modifications are made and what are the consequences for MeCP2 functions and the nervous system? In the past we found evidence that MeCP2 collaborates with CDKL5. In addition, we found that CDKL5 can phosphorylate MeCP2 in vitro and now we have mapped the specific target within MeCP2. Our results so far show that this particular modification of MeCP2 is mediated, at least in part, by CDKL5, that it occurs in activated neurons and that it causes the dissociation of MeCP2 from chromatin. Here we will characterize the signals causing this modification and its effects on MeCP2 functions regarding chromatin functions and neuronal development. We believe that these studies might explain how MeCP2 dysfunctions cause the RTT conditions and also provide further information of CDKL5 functions in the brain.

PROJECT DETAILS 

beginning: 2012.

end: 2013.

Country of research: Italy

Counry of funding source: United States

Funding organization: Inational Rett Syndrome Foundation

Financing: PRIVATE FUNDERS – 148 000 €

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