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- Title
Single Molecule Analysis of Serotonin Transporter Regulation Using Antagonist-Conjugated Quantum Dots Reveals Restricted, p38 MAPK-Dependent Mobilization Underlying Uptake Activation.
- Authors
Chang, Jerry C.; Tomlinson, Ian D.; Warnement, Michael R.; Ustione, Alessandro; Carneiro, Ana M. D.; Piston, David W.; Blakely, Randy D.; Rosenthal, Sandra J.
- Abstract
The presynaptic serotonin (5-HT) transporter (SERT) is targeted by widely prescribed antidepressant medications. Altered SERT expression or regulation has been implicated in multiple neuropsychiatric disorders, including anxiety, depression and autism. Here, we implement a generalizable strategy that exploits antagonist-conjugated quantum dots (Qdots) to monitor, for the first time, single SERT proteins on the surface of serotonergic cells. We document two pools of SERT proteins defined by lateral mobility, one that exhibits relatively free diffusion, and a second, localized to cholesterol and GM1 ganglioside-enriched microdomains, that displays restricted mobility. Receptor-linked signaling pathways that enhance SERT activity mobilize transporters that, nonetheless, remain confined to membranemicrodomains. Mobilization of transporters arises from a p38 MAPK-dependent untethering of the SERTC terminus from the juxtamembrane actin cytoskeleton. Our studies establish the utility of ligand-conjugated Qdots for analysis of the behavior of single membrane proteins and reveal a physical basis for signaling-mediated SERT regulation.
- Subjects
SEROTONIN; QUANTUM dots; MITOGEN-activated protein kinases; ANTIDEPRESSANTS; NEUROBEHAVIORAL disorders; ANXIETY; MENTAL depression
- Publication
Journal of Neuroscience, 2012, Vol 32, Issue 26, p8919
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0048-12.2012