Abstract
Many kinds of transporters contribute to glutamatergic excitatory synaptic transmission. Glutamate is loaded into synaptic vesicles by vesicular glutamate transporters to be released from presynaptic terminals. After synaptic vesicle release, glutamate is taken up by neurons or astrocytes to terminate the signal and to prepare for the next signal. Glutamate transporters on the plasma membrane are responsible for transporting glutamate from extracellular fluid to cytoplasm. Glutamate taken up by astrocyte is converted to glutamine by glutamine synthetase and transported back to neurons through glutamine transporters on the plasma membranes of the astrocytes and then on neurons. Glutamine is converted back to glutamate by glutaminase in the neuronal cytoplasm and then loaded into synaptic vesicles again. Here, the structures of glutamate transporters and glutamine transporters, their conformational changes, and how they use electrochemical gradients of various ions for substrate transport are summarized. Pharmacological regulations of these transporters are also discussed.
Highlights
Glutamate is the major excitatory neurotransmitter in our central nervous system
Vesicular glutamate transporters load glutamate into synaptic vesicles at presynaptic terminals
Glutamate released from presynaptic terminals to the synaptic clefts is removed by glutamate transporters on the plasma membrane of neurons and astrocytes (Figure 1)
Summary
Glutamate is the major excitatory neurotransmitter in our central nervous system. Vesicular glutamate transporters load glutamate into synaptic vesicles at presynaptic terminals. The glutamate clearance prevents neuronal excitotoxicity caused by excess activation of glutamate receptors. Both neurons and astrocytes express glutamate transporters for glutamate uptake. Glutamine is converted back to glutamate in neurons by glutaminase, and loaded into synaptic vesicles for another round of presynaptic release. This whole process is called the glutamate–glutamine cycle. All transporters working in the glutamate–glutamine cycle are membrane proteins which have multiple transmembrane helices These transporters are pseudo-symmetric and use an alternating access mechanism to transfer their substrates from one side of the membrane to the other. Their crystal structures reveal how they operate and how they are pharmacologically regulated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
