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Author Notes:

Correspondence: James Zheng, PhD, Department of Cell Biology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322. Tel: (404) 727-9133. Fax: (404) 727-6256. james.zheng@emory.edu

YR designed and performed a majority of the experiments in this study.

KRM acquired the data involving brain slices, KY and HCH contributed the electrophysiology data, AW made the gephyrin mutations, ALDB helped with experiments concerning GABAAR knockdown and discussion, HCH provided invaluable input to the manuscript, JQZ designed, oversaw, and wrote the manuscript with YR.

We would also like to thank other members of Zheng lab for their insightful discussion of the project and technical help


Research Funding:

This research was supported in part by grants from the National Institutes of Health to JQZ (GM083889, GM084363, and HD023315), HCH (GM60448 and EY114852), and ALDB (NS038752).

The work also received support from a pilot grant from Emory Alzheimer’s Disease Resource Center (ADRC P50 AG025688), a NINDS core facilities grant (P30NS055077) to the Neuronal Imaging Core of Emory Neuroscience, and a postdoctoral fellowship from the Ellison Medical Foundation/American Federation for Aging Research to YR.

Activity-Dependent Regulation of Dendritic Growth and Maintenance by Glycogen Synthase Kinase 3?


Journal Title:

Nature Communications


Volume 4


Type of Work:

Article | Final Publisher PDF


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 3β (GSK3β) regulates dendritic development in an activity-dependent manner. We find that GSK3β in somatodendritic compartments of hippocampal neurons becomes highly phosphorylated at serine-9 upon synaptogenesis. This phosphorylation-dependent GSK3β inhibition is mediated by neurotrophin signaling and is required for dendritic growth and arborization. Elevation of GSK3β activity leads to marked shrinkage of dendrites, whereas its inhibition enhances dendritic growth. We further show that these effects are mediated by GSK3β regulation of surface GABAA receptor levels via the scaffold protein gephyrin. GSK3β activation leads to gephyrin phosphorylation to reduce surface GABAA receptor clusters, resulting in neuronal hyperexcitability that causes dendrite shrinkage. These findings thus identify GSK3β as a key player in activity-dependent regulation of dendritic development by targeting the excitatory-inhibitory balance of the neuron.

Copyright information:

© 2013, Rights Managed by Nature Publishing Group

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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