Journal
ENEURO
Volume 5, Issue 1, Pages -Publisher
SOC NEUROSCIENCE
DOI: 10.1523/ENEURO.0203-17.2017
Keywords
GABAA receptor; homeostatic plasticity; PALM; post-translation modification; single particle tracking
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Funding
- INSERM
- Sorbonne Universite-UPMC
- LabEx Biopsy
- Olgamyenfisch Grant
- University of Zurich
- Universite Pierre and Marie Curie
- DIM NeRF from Region Ile-de-France
- FRC/Rotary 'Espoir en tete'
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Synaptic plasticity relies on the rapid changes in neurotransmitter receptor number at postsynaptic sites. Using superresolution photoactivatable localization microscopy imaging and quantum dot-based single-particle tracking in rat hippocampal cultured neurons, we investigated whether the phosphorylation status of the main scaffolding protein gephyrin influenced the organization of the gephyrin scaffold and GABA(A) receptor (GABA(A)R) membrane dynamics. We found that gephyrin phosphorylation regulates gephyrin microdomain compaction. Extracellular signal-regulated kinase 1/2 and glycogen synthase kinase 3 beta (GSK3 beta) signaling alter the gephyrin scaffold mesh differentially. Differences in scaffold organization similarly affected the diffusion of synaptic GABA(A)Rs, suggesting reduced gephyrin receptor-binding properties. In the context of synaptic scaling, our results identify a novel role of the GSK3 beta signaling pathway in the activity-dependent regulation of extrasynaptic receptor surface trafficking and GSK3 beta, protein kinase A, and calcium/calmodulin-dependent protein kinase II alpha pathways in facilitating adaptations of synaptic receptors.
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