期刊
JOURNAL OF NEUROSCIENCE
卷 35, 期 45, 页码 15127-15134出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1443-15.2015
关键词
dendrite; nuclear translocation; transcription; BDNF; neurotrophin; MeCP2
资金
- Research Grants Council of Hong Kong SAR [HKUST660810, HKUST661111, HKUST661212, HKUST660213]
- National Key Basic Research Program of China [2013CB530900]
- Hong Kong Research Grants Council Theme-based Research Scheme [T13-607/12R]
- SH Ho Foundation
The proper growth and arborization of dendrites in response to sensory experience are essential for neural connectivity and information processing in the brain. Although neuronal activity is important for sculpting dendrite morphology, the underlying molecular mechanisms are not well understood. Here, we report that cyclin-dependent kinase 5 (Cdk5)-mediated transcriptional regulation is a key mechanism that controls activity-dependent dendrite development in cultured rat neurons. During membrane depolarization, Cdk5 accumulates in the nucleus to regulate the expression of a subset of genes, including that of the neurotrophin brain-derived neurotrophic factor, for subsequent dendritic growth. Furthermore, Cdk5 function is mediated through the phosphorylation of methyl-CpG-binding protein 2, a key transcriptional repressor that is mutated in the mental disorder Rett syndrome. These findings collectively suggest that the nuclear import of Cdk5 is crucial for activity-dependent dendrite development by regulating neuronal gene transcription during neural development.
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