World Library  
Flag as Inappropriate
Email this Article

Glutamate transporter

Article Id: WHEBN0028312281
Reproduction Date:

Title: Glutamate transporter  
Author: World Heritage Encyclopedia
Language: English
Subject: Glutamic acid, Membrane transport protein, Excitotoxicity, Dopamine transporter, Moxidectin, Glutamate receptor, Ion transporter, Solute carrier family, Neurotransmitter transporter
Collection:
Publisher: World Heritage Encyclopedia
Publication
Date:
 

Glutamate transporter

Excitatory amino-acid transporters (EAATs), also known as glutamate transporters, belong to the family of neurotransmitter transporters. Glutamate is the principal excitatory neurotransmitter in the vertebrate brain. EAATs serve to terminate the excitatory signal by removal (uptake) of glutamate from the neuronal synapse into neuroglia and neurons.

The EAATs are membrane-bound secondary transporters that superficially resemble ion channels.[1] These transporters play the important role of regulating concentrations of glutamate in the extracellular space by transporting it along with other ions across cellular membranes.[2] After glutamate is released as the result of an action potential, glutamate transporters quickly remove it from the extracellular space to keep its levels low, thereby terminating the synaptic transmission.[1][3]

Without the activity of glutamate transporters, glutamate would build up and kill cells in a process called excitotoxicity, in which excessive amounts of glutamate acts as a toxin to neurons by triggering a number of biochemical cascades. The activity of glutamate transporters also allows glutamate to be recycled for repeated release.[4]

Glutamate transporters also transport aspartate and are present in virtually all peripheral tissues including bone, heart, liver, and testes. They exhibit stereoselectivity for L-glutamate but transport both L- and D-aspartate.

Classes

There are two general classes of glutamate transporters, those that are dependent on an electrochemical gradient of sodium ions (the EAATs) and those that are not (VGLUTs and xCT).[5] The cystine-glutamate antiporter (xCT) is localised to the plasma membrane of cells whilst vesicular glutamate transporters (VGLUTs) are found in the membrane of glutamate-containing synaptic vesicles. Na+-dependent EAATs are also dependent on transmembrane K+ and H+concentration gradients, and so are also known as 'sodium and potassium coupled glutamate transporters'. Na+-dependent transporters have also been called 'high-affinity glutamate transporters', though their glutamate affinity actually varies widely.[5]

Mitochondria also possess mechanisms for taking up glutamate that are quite distinct from membrane glutamate transporters.[5]

EAATs

In humans (as well as in rodents), five subtypes have been identified and named EAAT1-5 ( whereas the acronyms EAAT4 and EAAT5 are conserved.

When glutamate is taken up into glial cells by the EAATs, it is converted to glutamine and subsequently transported back into the presynaptic neuron, converted back into glutamate, and taken up into synaptic vesicles by action of the VGLUTs.[3][8] This process is named the glutamate-glutamine cycle.

The glial transporters - in particular the various splice variants of GLT-1 (EAAT2) - play the largest role (90%) in regulating extracellular glutamate concentration.[9]

protein gene tissue distribution
EAAT1 SLC1A3 glial and endothelial cells
EAAT2 SLC1A2 glial and endothelial cells
EAAT3 SLC1A1 neurons
EAAT4 SLC1A6 neurons
EAAT5 SLC1A7 retina
VGLUT1 SLC17A7 neurons
VGLUT2 SLC17A6 neurons
VGLUT3 SLC17A8 neurons

VGLUTs

Four types of vesicular glutamate transporters are known, VGLUTs 1–3[10] (SLC17A7, SLC17A6, and SLC17A8 respectively)[3] and the novel glutamate/aspartate transporter sialin.[11] These transporters pack the neurotransmitter into synaptic vesicles so that they can be released into the synapse. VGLUTs are dependent on the proton gradient that exists in the secretory system (vesicles being more acidic than the cytosol). VGLUTs have only between one hundredth and one thousandth the affinity for glutamate that EAATs have.[3] Also unlike EAATs, they do not appear to transport aspartate.

Pathology

Overactivity of glutamate transporters may result in inadequate synaptic glutamate and may be involved in schizophrenia and other mental illnesses.[1]

During injury processes such as ischemia and traumatic brain injury, the action of glutamate transporters may fail, leading to toxic buildup of glutamate. In fact, their activity may also actually be reversed due to inadequate amounts of adenosine triphosphate to power ATPase pumps, resulting in the loss of the electrochemical ion gradient. Since the direction of glutamate transport depends on the ion gradient, these transporters release glutamate instead of removing it, which results in neurotoxicity due to overactivation of glutamate receptors.[12]

Loss of the Na+-dependent glutamate transporter EAAT2 is suspected to be associated with neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, and ALS–parkinsonism dementia complex.[13] Also, degeneration of motor neurons in the disease amyotrophic lateral sclerosis has been linked to loss of EAAT2 from patients' brains and spinal cords.[13]

See also

References

External links

  • Medical Subject Headings (MeSH)

This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 



Copyright © World Library Foundation. All rights reserved. eBooks from World eBook Library are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.