高亲和力谷氨酸转运体结构和功能的研究进展

Progress in The Research of The Structure and Function of High-affinity Glutamate Transporters

真核生物高亲和力谷氨酸转运体(excitatory amino acid transporters,EAATs)分为GLAST(EAAT1)、GLT-1(EAAT2)、EAAC1(EAAT3)、EAAT4和EAAT5等5个亚型.高亲和力谷氨酸转运体结构学的研究,揭示了谷氨酸转运体的跨膜拓扑结构、真核和原核生物EAATs结构的差异,以及在底物转运过程中的一些底物和协同转运离子的结合位点.其功能学的研究发现,EAATs在参与突触的传递,避免兴奋性氨基酸的毒性效应中发挥重要作用,同时也参与了对学习、记忆以及运动行为的调控.结合我们既往的工作,就近几年EAATs的结构和功能研究做一综述.

Eukaryotic high-affinity glutamate transporters （also called excitatory amino acid transporters, EAATs） contain five isoforms, GLAST （EAAT1）, GLT-1 （EAAT2）, EAAC1 （EAAT3）, EAAT4 and EAAT5. Structural analysis reveal the membrane topology of glutamate transporters, the structural differences between the eukaryotic and prokaryotic glutamate transporters, and the binding sites for substrate and coupled ions during the transport cycle. Functional studies indicate that EAATs are involved in synaptic transmission, and EAATs play key roles in avoiding glutamate excitotoxicity. Besides, EAATs also participate in regulating learning, memory and motor behavior. In this review, combined with our previous work, we summarize the progress in the research of the structure and function of high-affinity glutamate transporters recently.