Journal of Biological Chemistry
Medical Sciences | Medicine and Health Sciences | Pharmacy and Pharmaceutical Sciences
Glutamate transporters maintain low synaptic concentrations of neurotransmitter by coupling uptake to flux of other ions. After cotransport of glutamic acid with Na+, the cycle is completed by countertransport of K+. We have identified an amino acid residue (glutamate 404) influencing ion coupling in a domain of the transporter implicated previously in kainate binding. Mutation of this residue to aspartate (E404D) prevents both forward and reverse transport induced by K+. Sodium-dependent transmitter exchange and a transporter-mediated chloride conductance are unaffected by the mutation, indicating that this residue selectively influences potassium flux coupling. The results support a kinetic model in which sodium and potassium are translocated in distinct steps and suggest that this highly conserved region of the transporter is intimately associated with the ion permeation pathway.
© 1997 by The American Society for Biochemistry and Molecular Biology, Inc.
Kavanaugh, Michael; Bendahan, Annie; Zerangue, Noa; Zhang, Yumin; and Kanner, Baruch I., "Mutation of an Amino Acid Residue Influencing Potassium Coupling in the Glutamate Transporter GLT-1 Induces Obligate Exchange" (1997). Biomedical and Pharmaceutical Sciences Faculty Publications. 55.