Activity- and sleep-dependent regulation of tonic inhibition by Shisa7
| Autor: | Yan Li, Wenyan Han, Kunwei Wu, Wei Lu, Qingjun Tian |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
α5 subunit Nerve Tissue Proteins Hippocampal formation Hippocampus General Biochemistry Genetics and Molecular Biology Exocytosis Article tonic inhibition 03 medical and health sciences GABA 0302 clinical medicine Homeostatic plasticity Serine Animals Homeostasis Humans Tonic (music) PKA Phosphorylation Wakefulness Receptor Protein kinase A lcsh:QH301-705.5 Mice Knockout Neurons GABAA receptor Chemistry Membrane Proteins Neural Inhibition Long-term potentiation Receptors GABA-A Cyclic AMP-Dependent Protein Kinases Mice Inbred C57BL 030104 developmental biology HEK293 Cells lcsh:Biology (General) Shisa7 Sleep Neuroscience 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Cell Reports, Vol 34, Iss 12, Pp 108899-(2021) Cell reports |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY Tonic inhibition mediated by extrasynaptic γ-aminobutyric acid type A receptors (GABAARs) critically regulates neuronal excitability and brain function. However, the mechanisms regulating tonic inhibition remain poorly understood. Here, we report that Shisa7 is critical for tonic inhibition regulation in hippocampal neurons. In juvenile Shisa7 knockout (KO) mice, α5-GABAAR-mediated tonic currents are significantly reduced. Mechanistically, Shisa7 is crucial for α5-GABAAR exocytosis. Additionally, Shisa7 regulation of tonic inhibition requires protein kinase A (PKA) that phosphorylates Shisa7 serine 405 (S405). Importantly, tonic inhibition undergoes activity-dependent regulation, and Shisa7 is required for homeostatic potentiation of tonic inhibition. Interestingly, in young adult Shisa7 KOs, basal tonic inhibition in hippocampal neurons is unaltered, largely due to the diminished α5-GABAAR component of tonic inhibition. However, at this stage, tonic inhibition oscillates during the daily sleep/wake cycle, a process requiring Shisa7. Together, these data demonstrate that intricate signaling mechanisms regulate tonic inhibition at different developmental stages and reveal a molecular link between sleep and tonic inhibition. Graphical abstract In brief Wu et al. discover a critical role of Shisa7 in the regulation of tonic inhibition in hippocampal neurons and find that PKA phosphorylates Shisa7 to modulate activity-dependent regulation of tonic inhibition. They also show that Shisa7 is involved in tonic inhibition regulation over the daily sleep/wake cycle. |
| Databáze: | OpenAIRE |
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