Anion conduction and secondary active glutamate transport by excitatory amino acid transporters
Excitatory amino acid transporters (EAATs) terminate glutamatergic synaptic transmission and control synaptic glutamate concentrations by moving the transmitter back from the synaptic cleft into surrounding cells. EAATs do not only represent the main glutamate re-uptake system in the mammalian brain; but they are also ligand-gated anion channels. Anion channel opening can only occur in certain transporter conformations, resulting in an intimate intertwining of glutamate transport and anion channel function. Using a combination of molecular simulations and functional studies, we aim to identify how EAATs transport glutamate, how they serve as anion-conducting channels, and how these channels open and close, with the ultimate aim to understand how EAAT transport and channel function are coupled to each other. Consequently, we will use our results to identify novel intermediate EAAT structures as potential drug targets and search for conformation-selective pharmacological agents. These studies might establish a basis for future correction of EAAT glutamate transport and anion conduction under pathological conditions.
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Prof. Dr. Christoph Fahlke
52425 Jülich
Dr. Jan-Philipp Machtens
52425 Jülich