Ion transport and regulation in a synaptic vesicle glutamate transporter

• DOI: 10.1126/science.aba9202
• Publication Date: 2020-05-21T23:02:25Z
• Authors: Fei Li; Jacob Eriksen; Janet Finer-Moore; Roger Chang; Phuong Nguyen; Alisa Bowen; Alexander Myasnikov; Zanlin Yu; David Bulkley; Yifan Cheng; Robert H. Edwards; Robert M. Stroud
• Keywords: 570; 0303 health sciences; Binding Sites; Ion Transport; General Science & Technology; 1.1 Normal biological development and functioning; Cryoelectron Microscopy; Neurosciences; Glutamic Acid; Biological Sciences; Hydrogen-Ion Concentration; Membrane Potentials; Rats; 03 medical and health sciences; Allosteric Regulation; Chlorides; Protein Domains; Chloride Channels; Vesicular Glutamate Transport Protein 2; Animals; Biochemistry and Cell Biology; Amino Acid Sequence; Synaptic Vesicles

Transport dependent on context

Transporter proteins move substrates across a membrane, often coupling this activity to cellular ion concentration gradients. For neurotransmitter transporters, which reside in synaptic vesicles that fuse with the plasma membrane after an action potential, transport activity needs to be regulated so that they do not pump out neurotransmitters after vesicle fusion. Using cryo–electron microscopy, Li et al. determined the structure of a vesicular glutamate transporter from rat that unveils some of the distinctive features that enable it to function properly in two distinct cellular environments. An allosteric pH sensor, proposed to be a glutamate residue, gates binding of the substrate glutamate and simultaneously permits binding and counterflow of chloride ions. This molecular traffic light allows for a single ion channel to behave appropriately in different contexts.

Science , this issue p. 893