Vesicle

Transporter

Neuroscience

Receptor

Electrophysiology

Serotonin

Serotonin transporter

Membrane

Biology

Reuptake

Gene

Biophysics

Synaptic vesicle

Chemistry

Hippocampus

Serotonin Plasma Membrane Transport Proteins

Antidepressant

Biochemistry

The Journal of General Physiology

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.

Serotonin transport in the 21st century