Activity-dependent inhibitory synapse scaling is determined by gephyrin phosphorylation and subsequent regulation of GABAA receptor diffusion
Abstract
Synaptic plasticity relies on the rapid changes in neurotransmitter receptor number at postsynaptic sites. Using super resolution PALM imaging and quantum-dot based single particle tracking in rat hippocampal cultured neurons, we investigated if the phosphorylation status of the main scaffolding protein gephyrin influenced the organization of the gephyrin scaffold and GABAA receptor (GABAAR) membrane dynamics. We found that gephyrin phosphorylation regulates gephyrin microdomain compaction. The ERK1/2 and GSK3 signaling alter the gephyrin scaffold mesh differentially. Differences in scaffold organization impacted similarly the diffusion of synaptic GABAARs, suggesting reduced gephyrin-receptor binding properties. In the context of synaptic scaling, our results identify a novel role of the GSK3 signaling pathway in the activity-dependent regulation of extrasynaptic receptor surface trafficking and GSK3PKA and CaMKII pathways in facilitating adaptations of synaptic receptors.
Domains
NeurobiologyOrigin | Files produced by the author(s) |
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