Protein Kinase C Activation Regulates Human Serotonin Transporters in HEK-293 Cells via Altered Cell Surface Expression
作者： Yan Qian , Aurelio Galli , Sammanda Ramamoorthy , Stefania Risso , Louis J. DeFelice
DOI: 10.1523/JNEUROSCI.17-01-00045.1997
关键词:
摘要: Antidepressant- and cocaine-sensitive serotonin (5-hydroxytryptamine, 5-HT) transporters (SERTs) dictate clearance of extracellular 5-HT after release. To explore protein kinase C-mediated SERT regulation, we generated a stable human (hSERT)-expressing cell line (293-hSERT) evaluated modulation activity via studies flux, hSERT-mediated currents under voltage clamp, surface distribution protein. 293-hSERT cells exhibit saturable, high-affinity, antidepressant-sensitive uptake as well hSERT-dependent whole-cell currents. In these cells, the C activator β-PMA caused time-dependent reduction in capacity ( V max) acute application SERT-mediated Effects were mimicked by phorbol ester β-PDBu, not observed with inactive α-isomers, could be blocked treatment inhibitor staurosporine. Biotinylation/immunoblot analyses showed that reductions are paralleled staurosporine-sensitive loss These data indicate altered abundance, rather than reduced catalytic transport efficiency, mediates PKC-dependent uptake.
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