Molecular physiology of EAAT anion channels
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- 作者：Christoph Fahlke ; Daniel Kortzak…
- 关键词：Glutamate transport ; Anion channel ; Molecular dynamics simulation ; Computational electrophysiology
- 刊名：Pfl¨¹gers Archiv - European Journal of Physiology
- 出版年：2016
- 出版时间：March 2016
- 年：2016
- 卷：468
- 期：3
- 页码：491-502
- 全文大小：3,157 KB
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Daniel Kortzak (1)
Jan-Philipp Machtens (1)
1. Institute of Complex Systems, Zelluläre Biophysik (ICS-4), Forschungszentrum Jülich, 52425, Jülich, Germany - 刊物主题：Human Physiology;
- 出版者：Springer Berlin Heidelberg
- ISSN：1432-2013
文摘
Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. After release from presynaptic nerve terminals, glutamate is quickly removed from the synaptic cleft by a family of five glutamate transporters, the so-called excitatory amino acid transporters (EAAT1–5). EAATs are prototypic members of the growing number of dual-function transport proteins: they are not only glutamate transporters, but also anion channels. Whereas the mechanisms underlying secondary active glutamate transport are well understood at the functional and at the structural level, mechanisms and cellular roles of EAAT anion conduction have remained elusive for many years. Recently, molecular dynamics simulations combined with simulation-guided mutagenesis and experimental analysis identified a novel anion-conducting conformation, which accounts for all experimental data on EAAT anion currents reported so far. We here review recent findings on how EAATs accommodate a transporter and a channel in one single protein. Keywords Glutamate transport Anion channel Molecular dynamics simulation Computational electrophysiology