| Author |
Landsberger, Nicoletta Bergo, Anna Barbiero, Isabella Strollo, Marta Gai, Marta Cobolli Gigli, Clementina Sertic, Sarah Stefanelli, Gilda Di Cunto, Ferdinando Kilstrup-nielsen, Charlotte |
| Description |
Author Affiliation: Bergo A ( From the Department of Theoretical and Applied Sciences, Section of Biomedical Research, University of Insubria, 21052 Busto Arsizio, Italy.); Strollo M ( From the Department of Theoretical and Applied Sciences, Section of Biomedical Research, University of Insubria, 21052 Busto Arsizio, Italy.); Gai M ( the Molecular Biotechnology Center, Department of Molecular Biotechnologies and Health Sciences, University of Turin, 10126 Turin, Italy.); Barbiero I ( From the Department of Theoretical and Applied Sciences, Section of Biomedical Research, University of Insubria, 21052 Busto Arsizio, Italy.); Stefanelli G ( From the Department of Theoretical and Applied Sciences, Section of Biomedical Research, University of Insubria, 21052 Busto Arsizio, Italy.); Sertic S ( the Department of Life Sciences, University of Milan, 20133 Milan, Italy, and.); Cobolli Gigli C ( the San Raffaele Rett Research Unit, Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy.); Di Cunto F ( the Molecular Biotechnology Center, Department of Molecular Biotechnologies and Health Sciences, University of Turin, 10126 Turin, Italy.); Kilstrup-Nielsen C ( From the Department of Theoretical and Applied Sciences, Section of Biomedical Research, University of Insubria, 21052 Busto Arsizio, Italy.); Landsberger N ( From the Department of Theoretical and Applied Sciences, Section of Biomedical Research, University of Insubria, 21052 Busto Arsizio, Italy, the San Raffaele Rett Research Unit, Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy landsben@uninsubria.it.) |
| Abstract |
Mutations in MECP2 cause a broad spectrum of neuropsychiatric disorders of which Rett syndrome 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 multifunctional protein that modulates its activity depending on its protein partners and posttranslational 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 (Tyr-120) whose relevance was suggested by a Rett syndrome patient carrying a Y120D substitution possibly mimicking a constitutively phosphorylated state. Unexpectedly, we found MeCP2 and its Tyr-120 phospho-isoform enriched at the centrosome both in dividing and postmitotic cells. The molecular and functional connection of MeCP2 to the centrosome was further reinforced through cellular and biochemical approaches. We show that, similar 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 the role of MeCP2 in cell growth and cytoskeleton stability and that might be relevant to understand some aspects of MeCP2-related conditions. Furthermore, they link the Tyr-120 residue and its phosphorylation to cell division, prompting future studies on the relevance of Tyr-120 for cortical development. |
