GluR2

GluR2

GluR2, also known as GluA2, is a subunit of the AMPA receptor, which is a type of ionotropic glutamate receptor in the central nervous system. AMPA receptors are responsible for fast synaptic transmission in the brain and are critical for synaptic plasticity, which underlies learning and memory.

Structure

GluR2 is one of four subunits (GluR1, GluR2, GluR3, and GluR4) that can combine to form AMPA receptors. Each subunit consists of an extracellular N-terminal domain, a ligand-binding domain, a transmembrane domain, and an intracellular C-terminal domain. The GluR2 subunit is particularly important because it influences the calcium permeability of the AMPA receptor.

Function

The presence of the GluR2 subunit in AMPA receptors is crucial for determining the receptor's permeability to calcium ions (Ca²⁺). AMPA receptors that include the GluR2 subunit are impermeable to calcium, whereas those lacking GluR2 are permeable to calcium. This is due to the presence of an arginine (R) residue in the pore-forming region of GluR2, which blocks calcium ions.

RNA Editing

GluR2 undergoes a unique post-transcriptional modification known as RNA editing. In the pre-mRNA of GluR2, a specific adenosine (A) is converted to inosine (I) by the enzyme adenosine deaminase acting on RNA (ADAR). This editing event changes a codon in the mRNA, resulting in the substitution of an arginine (R) for a glutamine (Q) in the protein. This Q/R site editing is essential for the calcium impermeability of GluR2-containing AMPA receptors.

Role in Disease

Alterations in GluR2 expression or RNA editing have been implicated in several neurological disorders. For example, reduced GluR2 expression or impaired RNA editing can lead to increased calcium permeability, which is associated with neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease.

Research and Therapeutic Implications

Understanding the role of GluR2 in synaptic transmission and plasticity has significant implications for developing treatments for neurological disorders. Modulating GluR2 expression or function could potentially be a therapeutic strategy for conditions characterized by excitotoxicity and calcium dysregulation.

See Also

• AMPA receptor
• Glutamate receptor
• RNA editing
• Neurodegenerative disease

References

• Hollmann, M., & Heinemann, S. (1994). Cloned glutamate receptors. Annual Review of Neuroscience, 17, 31-108.
• Seeburg, P. H., & Hartner, J. (2003). Regulation of ion channel/neurotransmitter receptor function by RNA editing. Current Opinion in Neurobiology, 13(3), 279-283.