KCC2 Gates Activity-Driven AMPA Receptor Traffic through Cofilin Phosphorylation
| Autor: | Quentin Chevy, Jean Christophe Poncer, Martin Heubl, Emmanuel Eugène, Marie Goutierre, Stéphanie Backer, Evelyne Bloch-Gallego, Imane Moutkine, Sabine Lévi |
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| Přispěvatelé: | Institut du Fer à Moulin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Dendritic spine
[SDV]Life Sciences [q-bio] [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Dendritic Spines AMPA receptor macromolecular substances Biology Hippocampus Exocytosis Rats Sprague-Dawley 03 medical and health sciences Actin remodeling of neurons 0302 clinical medicine Animals Receptors AMPA Enzyme Inhibitors RNA Small Interfering ComputingMilieux_MISCELLANEOUS Cells Cultured 030304 developmental biology Neurons 0303 health sciences Dose-Response Relationship Drug Symporters General Neuroscience Excitatory Postsynaptic Potentials Long-term potentiation Articles Cofilin Actin cytoskeleton Embryo Mammalian Actins Cell biology Rats Protein Transport Thiazoles Actin Depolymerizing Factors Doxycycline Thioglycolates Synaptic plasticity Silent synapse [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neuroscience Journal of Neuroscience, Society for Neuroscience, 2015, 35 (48), pp.15772-15786. ⟨10.1523/JNEUROSCI.1735-15.2015⟩ |
| ISSN: | 0270-6474 1529-2401 |
| Popis: | Expression of the neuronal K/Cl transporter KCC2 is tightly regulated throughout development and by both normal and pathological neuronal activity. Changes in KCC2 expression have often been associated with altered chloride homeostasis and GABA signaling. However, recent evidence supports a role of KCC2 in the development and function of glutamatergic synapses through mechanisms that remain poorly understood. Here we show that suppressing KCC2 expression in rat hippocampal neurons precludes long-term potentiation of glutamatergic synapses specifically by preventing activity-driven membrane delivery of AMPA receptors. This effect is independent of KCC2 transporter function and can be accounted for by increased Rac1/PAK- and LIMK-dependent cofilin phosphorylation and actin polymerization in dendritic spines. Our results demonstrate that KCC2 plays a critical role in the regulation of spine actin cytoskeleton and gates long-term plasticity at excitatory synapses in cortical neurons.SIGNIFICANCE STATEMENTChanges in the expression of neuronal chloride transporters, such as KCC2, occur during postnatal development and are induced in a variety of neurological and psychiatric conditions. Such changes are expected to primarily impact GABA signaling because GABAA receptors are predominantly permeable to chloride ions. However, the KCC2 transporter forms clusters near glutamatergic synapses and interacts with several actin-related proteins. We show that KCC2 is strictly required for LTP expression at hippocampal excitatory synapses. This effect is due to KCC2 interaction with the Rac1/PAK signaling pathway that controls actin polymerization. Suppressing this interaction promotes actin polymerization thereby hindering AMPA receptor traffic upon KCC2 suppression. Alterations of KCC2 expression therefore impact not only GABAergic signaling but also glutamatergic synaptic function and long term plasticity. |
| Databáze: | OpenAIRE |
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