Related Experiment Video
Updated: Jul 8, 2026

Selection of Transporter-Targeted Inhibitory Nanobodies by Solid-Supported-Membrane (SSM)-Based Electrophysiology
Published on: May 3, 2021
Bound to be different: neurotransmitter transporters meet their bacterial cousins
L Keith Henry1, Jens Meiler, Randy D Blakely
1Department of Pharmacology, Vanderbilt University Nashville, TN 37232-8548, USA. keith.henry@vanderbilt.edu
Abstract:
The neurotransmitter transporters belonging to the solute carrier 6 (SLC6) family, including the gamma-aminobutyric acid (GAT), norepinephrine (NET), serotonin (SERT) and dopamine (DAT) transporters are extremely important drug targets of great clinical relevance. These Na+, Cl(-)-dependent transporters primarily function following neurotransmission to reset neuronal signaling by transporting neurotransmitter out of the synapse and back into the pre-synaptic neuron. Recent studies have tracked down an elusive binding site for Cl(-) that facilitates neurotransmitter transport using structural differences evident with bacterial family members (e.g., the Aquifex aeolicus leucine transporter LeuT Aa) that lack Cl(-) dependence. Additionally, the crystal structures of antidepressant-bound LeuT Aa reveals a surprising mode of drug interaction that may have relevance for medication development. The study of sequence and structural divergence between LeuT Aa and human SLC6 family transporters can thus inform us as to how and why neurotransmitter transporters evolved a reliance on extracellular Cl(-) to propel the transport cycle; what residue changes and helical rearrangements give rise to recognition of different substrates; and how drugs such as antidepressants, cocaine, and amphetamines halt (or reverse) the transport process.
More Related Videos
13:16Characterization of Membrane Transporters by Heterologous Expression in E. coli and Production of Membrane Vesicles
Published on: December 31, 2019
06:18Brain Slice Biotinylation: An Ex Vivo Approach to Measure Region-specific Plasma Membrane Protein Trafficking in Adult Neurons
Published on: April 3, 2014
Related Concept Videos
ABC Transporters: Importer
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
The Significance of Membrane Transport
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
Neurochemical Transmission: Sites of Drug Action
Classification of Neurotransmitters
ABC Transporters: Exporter
Drugs Affecting Neurotransmitter Release or Uptake