Ion transport and regulation in a synaptic vesicle glutamate transporter

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