MeCP2 deficiency is associated with reduced levels of tubulin acetylation and can be restored using HDAC6 inhibitors
WA Gold, TA Lacina, LC Cantrill, John Christodoulou
JOURNAL OF MOLECULAR MEDICINE-JMM | SPRINGER HEIDELBERG | Published : 2015
UNLABELLED: Rett syndrome (RTT) is a severe neurodevelopmental disorder, predominantly caused by loss of function mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene. Despite the genetic cause being known in the majority of cases, the pathophysiology of the neurological phenotype of RTT is largely unknown. Tubulin and the microtubule network play an essential role in neuronal function whereby the acetylation state of microtubules dictates the efficiency of neuronal migration and differentiation, synaptic targeting and molecular motor trafficking of mRNA, high-energy mitochondria and brain-derived neurotrophic factor (BDNF)-containing vesicles. Recent reports have shown pertur..View full abstract
We thank Associate Professor James Eubanks of the University of Toronto, for many valuable discussions and Dr Zhaolan Zhou of the University of Pennsylvania, for supplying us with the initial breeding stock of the Mecp2<SUP>T158A</SUP> mouse model. This work was supported by the Rett Syndrome Association of New South Wales, Rett Syndrome Australian Research Fund, Rett Syndrome Association of Australia, International Rett Syndrome Foundation and Shire Human Genetic Therapies Inc (Lexington, MA, USA).