Journal
JOURNAL OF GENERAL PHYSIOLOGY
Volume 151, Issue 11, Pages 1248-1264Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1085/jgp.201812066
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Funding
- Fonds zur Forderung der Wissenschaftlichen Forschung [P 31813]
- National Institutes of Health [NS102277]
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Serotonin (5-hydroxytryptamine [5-HT]) is accumulated within nerve endings by the serotonin transporter (SERT), which terminates its extracellular action and provides cytoplasmic 5-HT for refilling of synaptic vesicles. SERT is the target for many antidepressant medications as well as psychostimulants such as cocaine and ecstasy (3,4-methylenedioxymethamphetamine). SERT belongs to the SLC6 family of ion-coupled transporters and is structurally related to several other transporter families. SERT was studied in the 1970s and 1980s using membrane vesicles isolated from blood platelets. These studies led to a proposed stoichiometry of transport that has been challenged by high-resolution structures of SERT and its homologues and by studies of SERT electrophysiology. Here, we review the original evidence alongside more recent structural and electrophysiological evidence. A self-consistent picture emerges with surprising insights into the ion fluxes that accompany 5-HT transport.
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