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

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 glu...

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Bibliographic Details
Published in:Neurochemical research 2016-03, Vol.41 (3), p.593-599
Main Authors: Cater, Rosemary J., Ryan, Renae M., Vandenberg, Robert J.
Format: Article
Language:English
Subjects:
Amino Acid Transport System X-AG - chemistry
Amino Acid Transport System X-AG - metabolism
Animals
Archaeal Proteins - chemistry
Archaeal Proteins - metabolism
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Chloride Channels - chemistry
Chloride Channels - metabolism
Molecular Dynamics Simulation
Neurochemistry
Neurology
Neurosciences
Original Paper
Protein Isoforms - chemistry
Protein Isoforms - metabolism
Protein Structure, Tertiary
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Summary: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.
ISSN:0364-3190
1573-6903
DOI:10.1007/s11064-015-1699-6