Methyl-CpG binding protein 2 (MeCP2) localizes at the centrosome and is required for proper mitotic spindle organization

Anna Bergo, Marta Strollo, Marta Gai, Isabella Barbiero, Gilda Stefanelli, Sarah Sertic, Clementina Cobolli Gigli, Ferdinando Di Cunto, Charlotte Kilstrup-Nielsen, Nicoletta Landsberger

Research output: Contribution to journalArticlepeer-review

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 dependingonits 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 studieson the relevance of Tyr-120 for cortical development.

Original languageEnglish
Pages (from-to)3223-3237
Number of pages15
JournalJournal of Biological Chemistry
Volume290
Issue number6
DOIs
Publication statusPublished - Feb 6 2015

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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