Postsynaptic Kainate Receptor Recycling and Surface Expression Are Regulated by Metabotropic Autoreceptor Signalling
| Autor: | Inmaculada M. González-González, Jeremy M. Henley |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
G-protein-coupled receptors
Kainate receptor Primaquine Biochemistry Hippocampus chemistry.chemical_compound 0302 clinical medicine Receptors Kainic Acid Structural Biology Postsynaptic potential synapse Egtazic Acid Autoreceptors Feedback Physiological 0303 health sciences Kainic Acid Long-term potentiation Endocytosis 3. Good health Cell biology Up-Regulation Protein Transport kainate receptor Excitatory postsynaptic potential Signal Transduction Receptor recycling Kainic acid glutamate receptor Dendritic Spines Endosomes Neurotransmission Biology Inhibitory postsynaptic potential 03 medical and health sciences neuronal transmission Genetics Animals Rats Wistar Molecular Biology 030304 developmental biology Benzophenanthridines Cell Membrane receptor recycling Cell Biology Original Articles neuron Rats chemistry Pertussis Toxin rab GTP-Binding Proteins Proteolysis Synapses 030217 neurology & neurosurgery |
| Zdroj: | Traffic (Copenhagen, Denmark) Traffic |
| ISSN: | 1600-0854 1398-9219 |
| Popis: | Kainate receptors (KARs) play fundamentally important roles in controlling synaptic function and regulating neuronal excitability. Postsynaptic KARs contribute to excitatory neurotransmission but the molecular mechanisms underlying their activity-dependent surface expression are not well understood. Strong activation of KARs in cultured hippocampal neurons leads to the downregulation of postsynaptic KARs via endocytosis and degradation. In contrast, low-level activation augments postsynaptic KAR surface expression. Here, we show that this increase in KARs is due to enhanced recycling via the recruitment of Rab11-dependent, transferrin-positive endosomes into spines. Dominant-negative Rab11 or the recycling inhibitor primaquine prevents the kainate-evoked increase in surface KARs. Moreover, we show that the increase in surface expression is mediated via a metabotropic KAR signalling pathway, which is blocked by the protein kinase C inhibitor chelerythrine, the calcium chelator BAPTA and the G-protein inhibitor pertussis toxin. Thus, we report a previously uncharacterized positive feedback system that increases postsynaptic KARs in response to low- or moderate-level agonist activation and can provide additional flexibility to synaptic regulation. |
| Databáze: | OpenAIRE |
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