Mutation of an amino acid residue influencing potassium coupling in the glutamate transporter GLT-1 induces obligate exchange

Michael P. Kavanaugh, Annie Bendahan, Noa Zerangue, Yumin Zhang, Baruch I. Kanner

Research output: Contribution to journalArticlepeer-review

154 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1703-1708
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number3
DOIs
StatePublished - 1997

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