Whole endosome recording shows that chloride interacts with vesicular glutamate transporters as both allosteric activator and permeant ion, and although the mode of permeation differs, chloride and glutamate use a related conduction pathway.
Cryo-EM structures of unliganded SLC1A5 and its complex with glutamine in outward-facing state provide insights into the substrate specificity and transport mechanism and will be helpful for developing selective inhibitors.
Crystal structures of an archaeal homologue of mammalian glutamate transporters in apo and ion-only bound outward- and inward-facing states reveal ion-coupled conformational changes supporting mechanisms of coupling, gating, and transport.
Sodium ions control the rates of both substrate binding and dissociation of an archaeal homologue of glutamate transporters in a manner that minimizes binding intermediates and maximizes transport efficiency.
In mammals, the vesicular glutamate transporter 1 acquired a proline-rich sequence that negatively regulates the spontaneous release of glutamate by reducing the exchange of synaptic vesicles along the axon.
Novel evidence on the molecular determinants of the dual function, anion permeation and substrate transport, of excitatory amino acid transporters opens avenues toward illuminating how these transporters regulate synaptic function and contribute to neurological conditions.
In central synapses, the mobility and supply of synaptic vesicles are determined by two independent biological factors: the morphological and structural organization of nerve terminals and the molecular signature of vesicles.