Chloride-dependent conformational changes in the GlyT1 glycine transporter

Abstract

Significance The NSS (neurotransmitter sodium symporter) or SLC6 family comprises a group of plasma membrane transport proteins that includes transporters for amino acid and amine neurotransmitters. Transporters in this family use transmembrane ion gradients as driving forces for intracellular accumulation of their substrates. Although all NSS transporters use Na + ions for transport, a large subset also requires Cl − ions. Na + is known to act at two sites on these proteins to stabilize an outward-open conformation and to interact with substrate to facilitate transition to an inward-open conformation, but the role of Cl − has not previously been established. We show here how Cl − acts independently from substrate to facilitate the conversion of an NSS transporter for glycine from outward- to inward-open states.