Activity-dependent regulation of dendritic growth and maintenance by glycogen synthase kinase 3?.

ABSTRACT: Activity-dependent dendritic development represents a crucial step in brain development, but its underlying mechanisms remain to be fully elucidated. Here we report that glycogen synthase kinase 3? (GSK3?) regulates dendritic development in an activity-dependent manner. We find that GSK3? in somatodendritic compartments of hippocampal neurons becomes highly phosphorylated at serine-9 upon synaptogenesis. This phosphorylation-dependent GSK3? inhibition is mediated by neurotrophin signalling and is required for dendritic growth and arbourization. Elevation of GSK3? activity leads to marked shrinkage of dendrites, whereas its inhibition enhances dendritic growth. We further show that these effects are mediated by GSK3? regulation of surface GABAA receptor levels via the scaffold protein gephyrin. GSK3? activation leads to gephyrin phosphorylation to reduce surface GABAA receptor clusters, resulting in neuronal hyperexcitability that causes dendrite shrinkage. These findings thus identify GSK3? as a key player in activity-dependent regulation of dendritic development by targeting the excitatory-inhibitory balance of the neuron.

SUBMITTER: Rui Y 

PROVIDER: S-EPMC3821971 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature