title: MeCP2 deficiency is associated with impaired microtubule stability.
abstract: Rett syndrome (RTT) is a neurodevelopmental disorder caused by MECP2 mutations. Previous studies performed on Mecp2-deficient brain showed striking changes in neuronal maturation. We recently showed that MeCP2 deficiency affects microtubule (MT) dynamics in RTT astrocytes. Here, we analyze MT stability in primary fibroblast cultures from patients with RTT syndrome and identify a significant decrease in stability compared to controls. Furthermore, we found that MT stability was reduced both in cells expressing the mutant or the wild-type allele in RTT fibroblasts, suggesting that mutated cells could damage wild-type ones through a non-cell-autonomous pathway. These results suggest that MeCP2 has a stabilizing role on MT dynamics and that its deficiency could lead to impaired MT stability that may explain in part the dendritic abnormalities observed in RTT brains.
authors.affiliation: Université Paris Descartes, CNRS UMR 8104, Institut Cochin, Laboratoire de Génétique des Maladies Neurodéveloppementales, Paris, France.
authors.forename: Chloé
authors.initials: C
authors.lastname: Delépine
authors.forename: Juliette
authors.initials: J
authors.lastname: Nectoux
authors.forename: Nadia
authors.initials: N
authors.lastname: Bahi-Buisson
authors.forename: Jamel
authors.initials: J
authors.lastname: Chelly
authors.forename: Thierry
authors.initials: T
authors.lastname: Bienvenu
mesh_terms: D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003080:Cold Temperature; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics; D015518:Rett Syndrome / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D050505:Mutant Proteins; D050257:Tubulin Modulators; D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human; D017239:Paclitaxel