The Split Personality of Glutamate Transporters: A Chloride Channel and a Transporter

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• 作者：Rosemary J. Cater ; Renae M. Ryan ; Robert J. Vandenberg
• 关键词：Glutamate transport ; EAAT ; SLC1 ; Anion conductance ; GltPh
• 刊名：Neurochemical Research
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：41
• 期：3
• 页码：593-599
• 全文大小：1,633 KB
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• 作者单位：Rosemary J. Cater (1)
  Renae M. Ryan (1)
  Robert J. Vandenberg (1)
  
  1. Discipline of Pharmacology, School of Medical Sciences and Bosch Institute, University of Sydney, Sydney, NSW, 2006, Australia
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Neurosciences
  Biochemistry
  Neurology
  
• 出版者：Springer Netherlands
• ISSN：1573-6903

文摘

Transporters and ion channels are conventionally categorised into distinct classes of membrane proteins. However, some membrane proteins have a split personality and can function as both transporters and ion channels. The excitatory amino acid transporters (EAATs) in particular, function as both glutamate transporters and chloride (Cl−) channels. The EAATs couple the transport of glutamate to the co-transport of three Na+ ions and one H+ ion into the cell, and the counter-transport of one K+ ion out of the cell. The EAAT Cl− channel is activated by the binding of glutamate and Na+, but is thermodynamically uncoupled from glutamate transport and involves molecular determinants distinct from those responsible for glutamate transport. Several crystal structures of an EAAT archaeal homologue, Glt_Ph, at different stages of the transport cycle, alongside numerous functional studies and molecular dynamics simulations, have provided extensive insights into the mechanism of substrate transport via these transporters. However, the molecular determinants involved in Cl− permeation, and the mechanism by which this channel is activated are not entirely understood. Here we will discuss what is currently known about the molecular determinants involved in EAAT-mediated Cl− permeation and the mechanisms that underlie their split personality.