Local miRNA-Dependent Translational Control of GABAAR Synthesis during Inhibitory Long-Term Potentiation
| Autor: | Joshua D. Garcia, Dipen Rajgor, Jennifer L. Sanderson, Theresa M. Welle, Mark L. Dell'Acqua, Alicia Purkey, Katharine R. Smith |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
GABAA receptor Chemistry Long-term potentiation Inhibitory postsynaptic potential General Biochemistry Genetics and Molecular Biology Cell biology Synapse 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Postsynaptic potential Synaptic plasticity medicine NMDA receptor Neuron 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports. 31:107785 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2020.107785 |
| Popis: | Molecular mechanisms underlying plasticity at brain inhibitory synapses remain poorly characterized. Increased postsynaptic clustering of GABAA receptors (GABAARs) rapidly strengthens inhibition during inhibitory long-term potentiation (iLTP). However, it is unclear how synaptic GABAAR clustering is maintained to sustain iLTP. Here, we identify a role for miR376c in regulating the translation of mRNAs encoding the synaptic α1 and γ2 GABAAR subunits, GABRA1 and GABRG2, respectively. Following iLTP induction, transcriptional repression of miR376c is induced through a calcineurin-NFAT-HDAC signaling pathway and promotes increased translation and clustering of synaptic GABAARs. This pathway is essential for the long-term expression of iLTP and is blocked by miR376c overexpression, specifically impairing inhibitory synaptic strength. Finally, we show that local de novo synthesis of synaptic GABAARs occurs exclusively in dendrites and in a miR376c-dependent manner following iLTP. Together, this work describes a local post-transcriptional mechanism that regulates inhibitory synaptic plasticity via miRNA control of dendritic protein synthesis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|