The uncoupled chloride conductance of a bacterial glutamate transporter homolog


Glutamate transporters (EAATs) are pivotal in mammalian synaptic transmission, tightly regulating synaptic levels of this excitatory neurotransmitter. In addition to coupled glutamate transport, the EAATs also show an uncoupled Cl conductance, whose physiological importance has recently been demonstrated. Little is yet known about the molecular mechanism of chloride permeation. Here we show that GltPh, a bacterial EAAT homolog whose structure has been determined, displays an uncoupled Cl conductance that can determine the rate of substrate uptake. A mutation analogous to one known to specifically affect Cl movement in EAAT1 has similar effects on GltPh, suggesting that this protein is an excellent structural model for understanding Cl permeation through the EAATs. We also observed an uncoupled Cl conductance in another bacterial EAAT homolog but not in a homolog of the Na+/Cl-coupled neurotransmitter transporters.

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Figure 1: GltPh has an uncoupled chloride conductance.
Figure 2: Anion dependence of aspartate transport.
Figure 3: Direct measurement of GltPh anion permeation.
Figure 4: GltPhS65V has altered anion permeation.
Figure 5: Chloride dependence of uptake in other bacterial transporters.


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We thank E. Gouaux (Vollum Institute and Howard Hughes Medical Institute, Oregon Health and Science University) for providing GltPh and LeuTAa plasmids, J. Lolkema (University of Groningen) for providing GltTBs plasmid, S. Singh and E. Gouaux for sharing unpublished results, K. Swartz for incisive comments on the manuscript and P. Curran for expert technical support. R.M.R. is funded by an Australian National Health and Medical Research Council C.J. Martin Postdoctoral Fellowship (ID358779). This work was supported by the US National Institute of Neurological Disorders and Stroke intramural program.

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Correspondence to Joseph A Mindell.

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Ryan, R., Mindell, J. The uncoupled chloride conductance of a bacterial glutamate transporter homolog. Nat Struct Mol Biol 14, 365–371 (2007).

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