The methyl-CpG binding protein 2 (MeCP2) localizes at the centrosome and is required for proper mitotic spindle organization [Cell Biology]

December 19th, 2014 by Bergo, A., Strollo, M., Gai, M., Barbiero, I., Stefanelli, G., Sertic, S., Cobolli Gigli, C., Di Cunto, F., Kilstrup-Nielsen, C., Landsberger, N.

Mutations in MECP2 cause a broad spectrum of neuropsychiatric disorders of which Rett syndrome (RTT) represents the best-defined condition; both neuronal and non-neuronal functions of the methyl-binding protein underlie the related pathologies. Nowadays, MeCP2 is recognized as a multi-functional protein that modulates its activity depending on its protein partners and post-translational modifications. However, we are still missing a comprehensive understanding of all MeCP2 functions and their involvement in the related pathologies. The study of human mutations often offers the possibility of clarifying the functions of a protein. Therefore, we decided to characterize a novel MeCP2 phospho-isoform (Y120) whose relevance was suggested by a RTT patient carrying a Y120D substitution, possibly mimicking a constitutively phosphorylated state. Unexpectedly, we found MeCP2 and its Y120 phospho-isoform enriched at the centrosome, both in dividing and post-mitotic cells. The molecular and functional connection of MeCP2 to the centrosome was further reinforced through cellular and biochemical approaches. We show that similarly to many centrosomal proteins, MeCP2 deficiency causes aberrant spindle geometry, prolonged mitosis and defects in microtubule nucleation. Collectively, our data indicate a novel function of MeCP2 that might reconcile previous data regarding MeCP2 role in cell growth and cytoskeleton stability and that might be relevant to understand some aspects of MeCP2-related conditions. Further, they link the Y120 residue and its phosphorylation to cell division prompting future studies on the relevance of Y120 for cortical development.