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

被引:152
作者
Kavanaugh, MP
Bendahan, A
Zerangue, N
Zhang, YM
Kanner, BI
机构
[1] HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT BIOCHEM,IL-91120 JERUSALEM,ISRAEL
[2] OREGON HLTH SCI UNIV,VOLLUM INST,PORTLAND,OR 97201
关键词
D O I
10.1074/jbc.272.3.1703
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:1703 / 1708
页数:6
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