Ryan Renae M, Mindell Joseph A
Membrane Transport Biophysics Unit, Porter Neuroscience Center, National Institute of Neurological Disorders and Stroke, US National Institutes of Health, 35 Convent Drive, Building 35, MSC 3701, Bethesda, Maryland 20892, USA.
Nat Struct Mol Biol. 2007 May;14(5):365-71. doi: 10.1038/nsmb1230. Epub 2007 Apr 15.
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 Glt(Ph), 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 Glt(Ph), 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.
谷氨酸转运体（EAATs）在哺乳动物突触传递中起关键作用，紧密调节这种兴奋性神经递质的突触水平。除了偶联的谷氨酸转运外，EAATs还表现出非偶联的Cl⁻电导，其生理重要性最近已得到证实。关于氯离子渗透的分子机制目前知之甚少。在这里，我们表明Glt(Ph)，一种其结构已被确定的细菌EAAT同源物，表现出一种非偶联的Cl⁻电导，它可以决定底物摄取的速率。一个类似于已知特异性影响EAAT1中Cl⁻移动的突变对Glt(Ph)有类似的影响，这表明该蛋白是理解Cl⁻通过EAATs渗透的优秀结构模型。我们还在另一种细菌EAAT同源物中观察到非偶联的Cl⁻电导，但在Na⁺/Cl⁻偶联神经递质转运体的同源物中未观察到。
