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Local miRNA-Dependent Translational Control of GABAAR Synthesis during Inhibitory Long-Term Potentiation.
Rajgor, Dipen; Purkey, Alicia M; Sanderson, Jennifer L; Welle, Theresa M; Garcia, Joshua D; Dell'Acqua, Mark L; Smith, Katharine R.
Afiliación
  • Rajgor D; Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Purkey AM; Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Sanderson JL; Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Welle TM; Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Garcia JD; Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Dell'Acqua ML; Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Smith KR; Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: katharine.r.smith@cuanschutz.edu.
Cell Rep ; 31(12): 107785, 2020 06 23.
Article en En | MEDLINE | ID: mdl-32579917
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biosíntesis de Proteínas / Potenciación a Largo Plazo / Receptores de GABA-A / MicroARNs Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biosíntesis de Proteínas / Potenciación a Largo Plazo / Receptores de GABA-A / MicroARNs Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos