How do glutamate transporters work?
Glutamate transporters are a family of neurotransmitter transporter proteins that move glutamate – the principal excitatory neurotransmitter – across a membrane. They exhibit stereoselectivity for L-glutamate but transport both L-aspartate and D-aspartate.
How is glutamate transported to the axon terminal?
Cytoplasmic glutamate is put into synaptic vesicles by vesicular glutamate transporter (VGlut) proteins and eventually released into the synaptic cleft when the vesicles fuse with the presynaptic plasma membrane.
Is glutamate transported across membranes?
As zwitterionic molecules, glutamate and aspartate are unable to diffuse across membranes. It is now well documented that uptake mechanisms have an important role in regulating the extracellular concentrations of glutamate and aspartate in the brain.
How does glutamate get into the cell?
They are secondary-active transporters, using the free energy stored in the transmembrane concentration gradient of Na+, which in turn is established by the sodium pump through hydrolysis of the primary energy source ATP, to take up glutamate into the cell against its own concentration gradient (11).
Is glutamate moved by axonal transport?
Neurofilaments are transported through axons by slow axonal transport. These results provide a molecular framework to link glutamate excitotoxicity with neurofilament accumulation seen in some neurodegenerative diseases.
Why is EAAT function so important for glutamate function?
The EAATs are membrane-bound pumps that closely resemble ion channels. These transporters play the important role of regulating concentrations of glutamate in the extracellular space, maintaining it at low physiological levels that promote biological function without promoting toxicity.
Is glutamate transported by axonal transport?
Neurofilaments are transported through axons by slow axonal transport. Excitotoxic mechanisms involving glutamate are believed to be part of the pathogenic process in some neurodegenerative diseases, but there is currently little evidence to link glutamate with neurofilament transport.
Can glutamate be transported in the blood?
In most regions of the brain, the uptake of glutamate and other anionic excitatory amino acids from the circulation is limited by the blood-brain barrier (BBB). Glutamate transport at the BBB has been studied by both in vitro cell uptake assays and in vivo perfusion methods.
What is Glutaminergic excitotoxicity?
Glutamate excitotoxicity is a cell death mechanism triggered by excessive glutamate release from neurons as well as glial cells. It was described almost 50 years ago as “a certain kind of regionally specific neuropathology” in the hypothalamus of infant mice (Olney, 1971).
What is the function of the vesicular glutamate transporter?
The vesicular glutamate transporter (VGLUT) is uniquely expressed in the vesicular membranes of glutamatergic cells. VGLUT utilizes a proton gradient, maintained by an ATP-dependent proton pump, to transport glutamate into the vesicle (see Box 16.2 for more details).
What is the mechanism of vesicular transport of a transmitter?
Indeed, the vesicular transport of most classical transmitters involves a mechanism of H (+) exchange, which restricts flux to acidic membranes such as synaptic vesicles.
What is the role of glutamate in excitatory neurotransmission?
Glutamate serves as the principal excitatory neurotransmitter. Release by exocytosis requires transport into synaptic vesicles by the vesicular glutamate transporters (VGLUTs), which are members of the solute carrier 17 (SLC17) gene family.
Do protons drive vesicular or non-vesicular excitatory transmission of glutamate?
However, vesicular transport of the principal excitatory transmitter glutamate depends primarily on membrane potential, which would drive non-vesicular efflux, and the role of protons is unclear.