Endocytosis Promotes Rapid Dopaminergic Signaling
| Autor: | F. Woodward Hopf, Sarah J. Kotowski, Mark von Zastrow, Antonello Bonci, Taban Seif |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Time Factors
G protein Dopamine Neuroscience(all) Endocytic cycle Action Potentials Biology Transfection Endocytosis Article Adenylyl cyclase chemistry.chemical_compound Cyclic AMP Animals Guanine Nucleotide Exchange Factors Humans RNA Small Interfering Receptor Cells Cultured Neurons Dose-Response Relationship Drug Receptors Dopamine D1 General Neuroscience HEK 293 cells Dopaminergic Hydrazones Benzazepines Embryo Mammalian Flow Cytometry Corpus Striatum Rats Cell biology Protein Transport Microscopy Fluorescence chemistry Dopamine receptor Dopamine Agonists Carrier Proteins Adenylyl Cyclases Signal Transduction |
| Zdroj: | Neuron. 71(2):278-290 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2011.05.036 |
| Popis: | D(1) dopamine receptors are primary mediators of dopaminergic signaling in the CNS. These receptors internalize rapidly following agonist-induced activation, but the functional significance of this process is unknown. We investigated D(1) receptor endocytosis and signaling in HEK293 cells and cultured striatal neurons using real-time fluorescence imaging and cAMP biosensor technology. Agonist-induced activation of D(1) receptors promoted endocytosis of receptors with a time course overlapping that of acute cAMP accumulation. Inhibiting receptor endocytosis blunted acute D(1) receptor-mediated signaling in both dissociated cells and striatal slice preparations. Although endocytic inhibition markedly attenuated acute cAMP accumulation, inhibiting the subsequent recycling of receptors had no effect. Further, D(1) receptors localized in close proximity to endomembrane-associated trimeric G protein and adenylyl cyclase immediately after endocytosis. Together, these results suggest a previously unanticipated role of endocytosis, and the early endocytic pathway, in supporting rapid dopaminergic neurotransmission. |
| Databáze: | OpenAIRE |
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