Molecular Playground/Glutamate Receptor

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One of the CBI Molecules being studied in the University of Massachusetts Amherst Chemistry-Biology Interface Program at UMass Amherst and on display at the Molecular Playground.

Rat glutamate receptor 2 complex with competitive agonist 3kg2

Contents

Glutamate Receptor

The AMPA glutamate receptor is a transmembrane protein located primarily at synapses that plays a critical role in communication between neurons. Our lab is interested in the AMPA receptor because strong evidence suggests that changes in location and amount of AMPA receptors at the synapse are central to learning and memory formation. At a molecular level, formation of memory is thought to be governed by changes at synapses between neurons in the brain through a process called long-term potentiation (LTP). One of the key changes involved in potentiation of a synapse is AMPA receptor insertion into the synapse and trafficking of receptors from extrasynaptic areas to the synapse. Studying receptor location and trafficking is one approach to better understanding the underlying changes that are linked to memory formation, and this is one of the primary goals of our lab.

AMPA receptors are iontropic glutamate receptors that allow cations, primarily sodium, to enter into the neuron when the receptor is bound to a ligand such as glutamate. The influx of positive ions depolarizes the membrane, bringing it closer to the threshold necessary for firing an action potential and passing the signal along the neuron to neighboring neurons. Each AMPA receptor is made up of some combination of four subunits, GluR1-4, and in an adult brain most of these receptors consist of GluR1 and Glur2 or Glur2 and Glur3, though other combinations are possible. Receptors containing the GluR2 subunit are calcium impermeable. The molecule on this page is a GluR2 homomer, an AMPA receptor made up of four GluR2 subunits.

Full view of the glutamate receptor shows the overall structure (amino-terminal, ligand-binding and transmembrane domains) in both (MF) and models.

Zooming in at the top of the receptor ()(RCB) one can view the amino terminal domain, which is a part of the extracellular domain. This domain is implicated in receptor assembly, trafficking, and localization.

Moving toward the bottom of the receptor () (SM) one can view the transmembrane domain. Here is the same domain separated from the rest of the protein..(DM) This domain widens in response to glutamate binding allowing for positive ions to pass through the post-synaptic membrane.

This view () highlights the area where a receptor antagonist, 2K200225, will bind.

Close up view of the ligand binding site ()(AH) of the endogenous ligand glutamate.

Molecular Playground banner: The glutamate receptor is found in the brain and allows neurons to communicate

3D structures of glutamate receptors

Glutamate Receptors

Additional Resources

For additional information, see: Alzheimer's Disease


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Proteopedia Page Contributors and Editors (what is this?)

Devon McCarthy, Rosie Combs-Bachmann, Mariel Feliciano, Steve McCarron, Amanda Hussey, Michal Harel, Jaime Prilusky, Lynmarie K Thompson, David Canner

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