View source for GRIA2

{{Short description|Mammalian protein found in Homo sapiens}}
{{redirect2|GluR2|Glutamate receptor 2|MGLUR2|Metabotropic glutamate receptor 2}}
{{Infobox_gene}}
'''Glutamate ionotropic receptor AMPA type subunit 2''' (Glutamate receptor 2, or GluR-2) is a [[protein]] that in humans is encoded by the ''GRIA2'' (or ''GLUR2'') [[gene]] and it is a subunit found in the [[AMPA receptor|AMPA receptors]].<ref name=HGNC>{{cite web |url=https://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=HGNC:4572 |title=Symbol Report: GRIA2 |author=HGNC |access-date=29 December 2017|author-link=HGNC }}</ref><ref name="pmid1311100">{{cite journal |vauthors=Sun W, Ferrer-Montiel AV, Schinder AF, McPherson JP, Evans GA, Montal M | title = Molecular cloning, chromosomal mapping, and functional expression of human brain glutamate receptors | journal = Proc Natl Acad Sci U S A | volume = 89 | issue = 4 | pages = 1443–7 |date=Mar 1992 | pmid = 1311100 | pmc = 48467 | doi =10.1073/pnas.89.4.1443  | bibcode = 1992PNAS...89.1443S | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: GRIA2 glutamate receptor, ionotropic, AMPA 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2891}}</ref>
== Function ==
[[Glutamate receptor]]s are the predominant excitatory [[neurotransmitter receptor]]s in the [[mammalian brain]] and are activated in a variety of normal neurophysiologic processes. This gene product belongs to a family of glutamate receptors that are sensitive to [[AMPA|alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate]] (AMPA), called [[AMPA receptor|AMPA receptors]], and function as [[Ligand-gated ion channel#Ionotropic glutamate receptors|ligand-activated cation channels]]. These channels are assembled from a combination of 4 subunits, encoded by 4 genes (''GRIA1-4''). The subunit encoded by this gene (''GRIA2'') is subject to [[RNA editing]] which renders the receptor that it becomes part of impermeable to [[Calcium in biology|calcium ions]] (Ca<sup>2+</sup>). Human and animal studies suggest that the RNA editing is essential for normal brain function, and defective RNA editing of this gene may be relevant to the etiology of [[amyotrophic lateral sclerosis]] (ALS). [[Alternative splicing]], resulting in transcript variants encoding different [[Protein isoform|isoforms]], has been noted for this gene, which includes the generation of flip and flop isoforms that vary in their [[signal transduction]] properties.<ref>{{Cite journal|last1=Hideyama|first1=Takuto|last2=Kwak|first2=Shin|date=2011|title=When Does ALS Start? ADAR2-GluA2 Hypothesis for the Etiology of Sporadic ALS|journal=Frontiers in Molecular Neuroscience|volume=4|pages=33|doi=10.3389/fnmol.2011.00033|issn=1662-5099|pmc=3214764|pmid=22102833|doi-access=free}}</ref><ref name="entrez" />
== Interactions ==
GRIA2 has been shown to [[Protein-protein interaction|interact]] with [[SPTAN1]],<ref name="pmid10576550">{{cite journal |vauthors=Hirai H, Matsuda S | title = Interaction of the C-terminal domain of delta glutamate receptor with spectrin in the dendritic spines of cultured Purkinje cells | journal = Neurosci. Res. | volume = 34 | issue = 4 | pages = 281–7 |date=September 1999 | pmid = 10576550 | doi = 10.1016/S0168-0102(99)00061-9  | s2cid = 45794233 }}</ref> [[GRIP1 (gene)|GRIP1]]<ref name="pmid11891216">{{cite journal |vauthors=Hirbec H, Perestenko O, Nishimune A, Meyer G, Nakanishi S, Henley JM, Dev KK | title = The PDZ proteins PICK1, GRIP, and syntenin bind multiple glutamate receptor subtypes. Analysis of PDZ binding motifs | journal = J. Biol. Chem. | volume = 277 | issue = 18 | pages = 15221–4 |date=May 2002 | pmid = 11891216 | doi = 10.1074/jbc.C200112200  | doi-access = free | hdl = 2262/89271 | hdl-access = free }}</ref> and [[PICK1]].<ref name=pmid11891216/>
== RNA editing ==
Several ion channels and neurotransmitters receptors pre-[[messenger RNA|mRNA]] as substrates for [[ADAR]]s. This includes 5 subunits of the glutamate receptor ionotropic AMPA glutamate receptor subunits (Glur2, Glur3, Glur4) and [[kainate receptor]] subunits (Glur5, Glur6). Glutamate-gated ion channels are made up of four subunits per channel, with each subunit contributing to the pore loop structure. The pore loop structure is related to that found in K<sup>+</sup> channels (e.g., human [[Kv1.1|K<sub>v</sub>1.1]] channel).<ref name="pmid11430906">{{cite journal |vauthors=Seeburg PH, Single F, Kuner T, Higuchi M, Sprengel R | title = Genetic manipulation of key determinants of ion flow in glutamate receptor channels in the mouse | journal = Brain Res. | volume = 907 | issue = 1–2 | pages = 233–43 |date=July 2001 | pmid = 11430906 | doi =10.1016/S0006-8993(01)02445-3  | s2cid = 11969068 }}</ref> The human K<sub>v</sub>1.1 channel pre mRNA is also subject to A to I RNA editing.<ref name="pmid15361858">{{cite journal |vauthors=Bhalla T, Rosenthal JJ, Holmgren M, Reenan R | title = Control of human potassium channel inactivation by editing of a small mRNA hairpin | journal = Nat. Struct. Mol. Biol. | volume = 11 | issue = 10 | pages = 950–6 |date=October 2004 | pmid = 15361858 | doi = 10.1038/nsmb825 | s2cid = 34081059 }}</ref> The function of the glutamate receptors is in the mediation of fast neurotransmission to the brain. The diversity of the subunits is determined, as well as RNA splicing by RNA editing events of the individual subunits. This give rise to the necessarily high diversity of these receptors. Glur2 is a gene product of the pre-mRNA of the GRIA2 gene and subject to RNA editing.
=== Type ===
The type of RNA editing that occurs in the pre-mRNA of GluR-2 is Adenosine-to-Inosine (A-to-I) editing. [11]
A-to-I RNA editing is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate them to inosine. Inosines are recognised as guanosine by the cells translational machinery. There are three members of the ADAR family ADARs 1-3, with ADAR1 and ADAR2 being the only enzymatically active members. ADAR3 is thought to have a regulatory role in the brain. ADAR1 and ADAR2 are widely expressed in tissues, while ADAR3 is restricted to the brain. The double-stranded regions of RNA are formed by base-pairing between residues in the close to region of the editing site, with residues usually in a neighboring intron, but can be an exonic sequence. The region that base pairs with the editing region is known as an Editing Complementary Sequence (ECS).
ADARs bind interact directly with the dsRNA substrate via their double-stranded RNA binding domains. If an editing site occurs within a coding sequence, it can result in a codon change. This can lead to translation of a protein isoform due to a change in its primary protein structure. Therefore, editing can also alter protein function. A-to-I editing occurs in a non coding RNA sequences such as introns, untranslated regions (UTRs), LINEs, SINEs (especially Alu repeats). The function of A to I editing in these regions is thought to involve creation of splice sites and retention of RNAs in the nucleus amongst others.
=== Location ===
In the pre-mRNA of GluR-2 the editing site Q/R is found at amino acid  position 607. This location is in the pore loop region deep within the ion channel in the proteins membrane segment 2. Editing results in a change from a glutamine(Q) codon to an Arginine (R) codon.
Editing at the R/G site, located at amino acid position 764 results in a codon change from arginine to glycine.  <!--R/G site is found in the -->
All editing in glutamate receptors occurs in double-stranded RNAs (dsRNAs), which form due to complementary base pairing between the region of the editing site within the exon and an ECS within an intron sequence.<ref name="pmid7937939">{{cite journal |vauthors=Egebjerg J, Kukekov V, Heinemann SF | title = Intron sequence directs RNA editing of the glutamate receptor subunit GluR2 coding sequence | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 91 | issue = 22 | pages = 10270–4 |date=October 1994 | pmid = 7937939 | pmc = 45001 | doi =10.1073/pnas.91.22.10270 | bibcode = 1994PNAS...9110270E | doi-access = free }}</ref>
R/G site
=== Conservation ===
=== Regulation ===
Editing occurs at the Q/R site at a frequency of 100% of GluR2 transcripts in the brain.  It is the only known editing site to be edited at a frequency of 100%.<ref name="pmid11430906"/> However some striatal and cortical neurons are edited less frequently. This has been suggested as a reason for the higher level of excitotoxicity of these particular neurons.<ref name="pmid11414791">{{cite journal |vauthors=Kim DY, Kim SH, Choi HB, Min C, Gwag BJ | title = High abundance of GluR1 mRNA and reduced Q/R editing of GluR2 mRNA in individual NADPH-diaphorase neurons | journal = Mol. Cell. Neurosci. | volume = 17 | issue = 6 | pages = 1025–33 |date=June 2001 | pmid = 11414791 | doi = 10.1006/mcne.2001.0988 | s2cid = 15351461 | url = http://repository.ajou.ac.kr/handle/201003/3753 }}</ref> The R/G site is developmentally regulated, being largely unedited in the embryonic brain with levels rising after birth. (ref 53)
=== Consequences ===
==== Structure ====
Editing results in a codon change from a glutamine codon (CAG) to an arginine codon (CIG).<ref name="pmid1717158">{{cite journal |vauthors=Sommer B, Köhler M, Sprengel R, Seeburg PH | title = RNA editing in brain controls a determinant of ion flow in glutamate-gated channels | journal = Cell | volume = 67 | issue = 1 | pages = 11–9 |date=October 1991 | pmid = 1717158 | doi =10.1016/0092-8674(91)90568-J | s2cid = 22029384 }}</ref> Editing at R/G results in a codon change.  The region of the editing site is known to be the region that controls divalent cation permeability. The other ionotropic AMPA glutamate receptors have a genomically encoded have a glutamine residue, while GluR2 has an arginine.
==== Function ====
RNA editing of the GluR-2 (GluR-B) pre-mRNA is the best-characterised example of A-to-I editing. Activated by L-Glutamate, a major excitatory neurotransmitter in vertebrates central nervous systems, it acts as an agonist at NMDA, AMPA, and kainate neurotransmitters.(103) Activation results in neuronal cation entry (CA2+), causing membrane depolarisation required for the process of excitatory neurotransmission.
The calcium permeability of these receptor channels is required for many important events in the CNS, including long-term potentiation.(104)
Since editing occurs in nearly 100% of transcripts and is necessary for life, it is often wondered why edited GluR-B is not genomically encoded instead of being derived by RNA editing. The answer is unknown.
RNA editing at the Q/R site is thought to alter the permeability of the channel rendering it impermeable to Ca<sup>2+</sup>. The Q/R site also occurs in the Kainate receptors GluR5 and GluR6.  Editing at the Q/R site determines the calcium permeability of the channel,<ref name="pmid11430906" /> with channels containing the edited form being less permeable to calcium. This differs from GluR6 where editing of the Q/R site may increase calcium permeability of the channel especially if the I/V and Y/C sites are also edited. Therefore, the main function of editing is therefore in regulation of electrophysiology of the channel.<ref name="pmid7678465">{{cite journal |vauthors=Egebjerg J, Heinemann SF | title = Ca2+ permeability of unedited and edited versions of the kainate selective glutamate receptor GluR6 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 90 | issue = 2 | pages = 755–9 |date=January 1993 | pmid = 7678465 | pmc = 45744 | doi =10.1073/pnas.90.2.755  | bibcode = 1993PNAS...90..755E | doi-access = free }}</ref>
Editing in some striatal and cortical neurons is more likely to be subject to excitotoxicity, thought to be due to less than 100% editing of these particular neurons.<ref name="pmid11414791"/> Editing also has several other function effects.  Editing alters the maturation and assembly of the channel, with the unedited form having a tendency to tetramerize and then is transported to the synapse.  However, the edited version is assembled as a monomer and resides mainly in the [[endoplasmic reticulum]]. The arginine residue in the pore loop of GluR-2 receptor is thought to belong to a retention signal for the endoplasmic reticulum. Therefore, editing - since it occurs at 100% frequency - inhibits the availability of the channel at the synapse. This process occurs before assembly of the channels, thereby preventing glur-2-forming homeric channels, which could interfere with synaptic signalling.
Editing also occurs at the R/G site. Editing at the R/G sites results in variation in the rate that the receptor recovers from desensitisation. Editing at these sites results in faster recovery time from desensitisation <ref name="pmid12062022">{{cite journal |vauthors=Greger IH, Khatri L, Ziff EB | title = RNA editing at arg607 controls AMPA receptor exit from the endoplasmic reticulum | journal = Neuron | volume = 34 | issue = 5 | pages = 759–72 |date=May 2002 | pmid = 12062022 | doi =10.1016/S0896-6273(02)00693-1  | s2cid = 15936250 | doi-access = free }}</ref>
==== Dysregulation ====
''' Amyotrophic Lateral Sclerosis  '''
Many human and animal studies have determined that RNA editing of the Q/R site in GluR2 pre-mRNA is necessary for normal brain function. Defective editing has been linked to several conditions such as [[amyotrophic lateral sclerosis]] (ALS). ALS effects 1 in 2000 people, usually fatal in 1–5 years, with onset in the majority of cases being sporadic and minority being familial.<ref name="pmid11715057">{{cite journal |vauthors=Cleveland DW, Rothstein JD |title=From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS |journal=[[Nat. Rev. Neurosci.]] |volume=2 |issue=11 |pages=806–19 |date=November 2001 |pmid=11715057 |doi=10.1038/35097565|s2cid=2050462 }}</ref> With these conditions motor neurons degenerate leading to eventual paralysis and respiratory failure. Glutamate excitotoxicity  is known to contribute to the spread of the  sporadic condition. Glutamate levels are increased up 40%, suggesting that activation of glutamate receptors could be the reason for this causing increase Ca influx and then neuronal death.<ref name="pmid11790386">{{cite journal  |vauthors=Spreux-Varoquaux O, Bensimon G, Lacomblez L, etal |title=Glutamate levels in cerebrospinal fluid in amyotrophic lateral sclerosis: a reappraisal using a new HPLC method with coulometric detection in a large cohort of patients |journal=[[J. Neurol. Sci.]] |volume=193 |issue=2 |pages=73–8 |date=January 2002 |pmid=11790386 |doi= 10.1016/S0022-510X(01)00661-X|s2cid=25556626 }}</ref> Since decrease nor loss of editing at Q/R site would lead to increase in calcium permeability. In diseased motor neurons editing levels of Glur 2 (62-100%) at this site was discovered to be reduced.<ref name="pmid15624111">{{cite journal |vauthors=Kwak S, Kawahara Y |title=Deficient RNA editing of GluR2 and neuronal death in amyotropic lateral sclerosis |journal=[[J. Mol. Med.]] |volume=83 |issue=2 |pages=110–20 |date=February 2005 |pmid=15624111 |doi=10.1007/s00109-004-0599-z|s2cid=2255590 }}</ref><ref name="pmid14985749">{{cite journal |vauthors=Kawahara Y, Ito K, Sun H, Aizawa H, Kanazawa I, Kwak S |title=Glutamate receptors: RNA editing and death of motor neurons |journal=[[Nature (journal)|Nature]] |volume=427 |issue=6977 |pages=801 |date=February 2004 |pmid=14985749 |doi=10.1038/427801a|bibcode=2004Natur.427..801K |s2cid=4310256 |doi-access=free }}</ref><ref name="pmid12694394">{{cite journal  |vauthors=Kawahara Y, Kwak S, Sun H, etal |title=Human spinal motoneurons express low relative abundance of GluR2 mRNA: an implication for excitotoxicity in ALS |journal=[[J. Neurochem.]] |volume=85 |issue=3 |pages=680–9 |date=May 2003 |pmid=12694394 |doi= 10.1046/j.1471-4159.2003.01703.x|s2cid=5997020 |doi-access= }}</ref><ref name="pmid16183555">{{cite journal |vauthors=Kawahara Y, Kwak S |title=Excitotoxicity and ALS: what is unique about the AMPA receptors expressed on spinal motor neurons? |journal= Amyotrophic Lateral Sclerosis|volume=6 |issue=3 |pages=131–44 |date=September 2005 |pmid=16183555 |doi=10.1080/14660820510037872 |s2cid=6640926 }}</ref>
Abnormal editing is thought to be specific for this condition, as editing levels have not been found to be decreased in spinal and bulbar muscular atrophy.<ref name="pmid16183555"/> Q/R editing is not the only mechanism involved, as editing occurs only in spinal motor neurons not in upper spinal neurons.  Also, it is unknown whether editing dysregulation is involved in the initiation of the condition, or whether it occurs during pathogenesis.
''' Epilepsy '''
In mouse models, failure of editing leads to epileptic seizures and death within 3 weeks of birth. <ref name="pmid11430906"/> Why editing exists at this site instead of a genomically encoded arginine is unknown since nearly 100% of transcripts are edited.
''' Cancer '''
Decreased editing at the Q/R site is also found in some human brain tumors.  Reduction of ADAR2 expression is thought to be associated with epileptic seizures in malignant glioma.<ref name="pmid11717408">{{cite journal |vauthors=Maas S, Patt S, Schrey M, Rich A | title = Underediting of glutamate receptor GluR-B mRNA in malignant gliomas | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 25 | pages = 14687–92 |date=December 2001 | pmid = 11717408 | pmc = 64742 | doi = 10.1073/pnas.251531398  | bibcode = 2001PNAS...9814687M | doi-access = free }}</ref>
== Use in diagnostic immunochemistry ==
GRIA2 is a diagnostic immunochemical marker for [[solitary fibrous tumour]] (SFT), distinguishing it from most mimics. Among other [[CD34]]-positive tumours, GRIA2 is also expressed in [[dermatofibrosarcoma protuberans]] ([[DFSP]]); however, clinical and histologic features aid in their distinction. GRIA2 shows a limited distribution in other soft tissue tumours.<ref>{{Cite journal
| pmid = 24456377
| year = 2014
| last1 = Vivero
| first1 = M
| title = GRIA2 is a Novel Diagnostic Marker for Solitary Fibrous Tumour Identified through Gene Expression Profiling
| journal = Histopathology
| pages = 71–80
| last2 = Doyle
| first2 = L. A.
| last3 = Fletcher
| first3 = C. D.
| last4 = Mertens
| first4 = F
| last5 = Hornick
| first5 = J. L.
| doi = 10.1111/his.12377
| volume=65
| issue=1
| s2cid = 42812062
}}</ref>
== See also ==
* [[AMPA receptor]]
== References ==
{{reflist}}
== Further reading ==
{{refbegin | 2}}
*{{cite journal   |vauthors=Soundarapandian MM, Tu WH, Peng PL, etal |title=AMPA receptor subunit GluR2 gates injurious signals in ischemic stroke. |journal=Mol. Neurobiol. |volume=32 |issue= 2 |pages= 145–55 |year= 2007 |pmid= 16215279 |doi=10.1385/MN:32:2:145  |title-link=Metabotropic glutamate receptor 2 |s2cid=21618951 }}
*{{cite journal   |vauthors=McNamara JO, Eubanks JH, McPherson JD, etal |title=Chromosomal localization of human glutamate receptor genes. |journal=J. Neurosci. |volume=12 |issue= 7 |pages= 2555–62 |year= 1992 |pmid= 1319477 |pmc=6575855 |doi=  10.1523/JNEUROSCI.12-07-02555.1992}}
*{{cite journal   |vauthors=Sommer B, Keinänen K, Verdoorn TA, etal |title=Flip and flop: a cell-specific functional switch in glutamate-operated channels of the CNS. |journal=Science |volume=249 |issue= 4976 |pages= 1580–5 |year= 1990 |pmid= 1699275 |doi=10.1126/science.1699275  |bibcode=1990Sci...249.1580S }}
*{{cite journal  |vauthors=Sommer B, Köhler M, Sprengel R, Seeburg PH |title=RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. |journal=Cell |volume=67 |issue= 1 |pages= 11–9 |year= 1991 |pmid= 1717158 |doi=10.1016/0092-8674(91)90568-J  |s2cid=22029384 }}
*{{cite journal  |vauthors=Paschen W, Hedreen JC, Ross CA |title=RNA editing of the glutamate receptor subunits GluR2 and GluR6 in human brain tissue. |journal=J. Neurochem. |volume=63 |issue= 5 |pages= 1596–602 |year= 1994 |pmid= 7523595 |doi=10.1046/j.1471-4159.1994.63051596.x  |s2cid=25226376 }}
*{{cite journal  |vauthors=Köhler M, Kornau HC, Seeburg PH |title=The organization of the gene for the functionally dominant alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor subunit GluR-B. |journal=J. Biol. Chem. |volume=269 |issue= 26 |pages= 17367–70 |year= 1994 |doi=10.1016/S0021-9258(17)32444-4 |pmid= 7545935 |doi-access=free }}
*{{cite journal   |vauthors=Eastwood SL, Burnet PW, Beckwith J, etal |title=AMPA glutamate receptors and their flip and flop mRNAs in human hippocampus. |journal=NeuroReport |volume=5 |issue= 11 |pages= 1325–8 |year= 1994 |pmid= 7919190 |doi=10.1097/00001756-199406270-00007  }}
*{{cite journal  |vauthors=Sun W, Ferrer-Montiel AV, Montal M |title=Primary structure and functional expression of the AMPA/kainate receptor subunit 2 from human brain. |journal=NeuroReport |volume=5 |issue= 4 |pages= 441–4 |year= 1994 |pmid= 8003671 |doi=10.1097/00001756-199401120-00018  }}
*{{cite journal   |vauthors=Higuchi M, Single FN, Köhler M, etal |title=RNA editing of AMPA receptor subunit GluR-B: a base-paired intron-exon structure determines position and efficiency. |journal=Cell |volume=75 |issue= 7 |pages= 1361–70 |year= 1994 |pmid= 8269514 |doi=10.1016/0092-8674(93)90622-W  |s2cid=25420811 }}
*{{cite journal  |vauthors=McLaughlin DP, Cheetham ME, Kerwin RW |title=Expression of alternatively-spliced glutamate receptors in human hippocampus. |journal=Eur. J. Pharmacol. |volume=244 |issue= 1 |pages= 89–92 |year= 1993 |pmid= 8420792 |doi=10.1016/0922-4106(93)90062-E  }}
*{{cite journal   |vauthors=Srivastava S, Osten P, Vilim FS, etal |title=Novel anchorage of GluR2/3 to the postsynaptic density by the AMPA receptor-binding protein ABP. |journal=Neuron |volume=21 |issue= 3 |pages= 581–91 |year= 1998 |pmid= 9768844 |doi=10.1016/S0896-6273(00)80568-1  |s2cid=14448034 |doi-access=free }}
*{{cite journal  |vauthors=Matsuda S, Mikawa S, Hirai H |title=Phosphorylation of serine-880 in GluR2 by protein kinase C prevents its C terminus from binding with glutamate receptor-interacting protein. |journal=J. Neurochem. |volume=73 |issue= 4 |pages= 1765–8 |year= 1999 |pmid= 10501226 |doi=10.1046/j.1471-4159.1999.731765.x  |s2cid=39402443 |doi-access= }}
*{{cite journal  |vauthors=Hirai H, Matsuda S |title=Interaction of the C-terminal domain of delta glutamate receptor with spectrin in the dendritic spines of cultured Purkinje cells. |journal=Neurosci. Res. |volume=34 |issue= 4 |pages= 281–7 |year= 2000 |pmid= 10576550 |doi=10.1016/S0168-0102(99)00061-9  |s2cid=45794233 }}
*{{cite journal  |vauthors=Aruscavage PJ, Bass BL |title=A phylogenetic analysis reveals an unusual sequence conservation within introns involved in RNA editing. |journal=RNA |volume=6 |issue= 2 |pages= 257–69 |year= 2000 |pmid= 10688364 |doi=10.1017/S1355838200991921  | pmc=1369911  }}
*{{cite journal   |vauthors=Osten P, Khatri L, Perez JL, etal |title=Mutagenesis reveals a role for ABP/GRIP binding to GluR2 in synaptic surface accumulation of the AMPA receptor. |journal=Neuron |volume=27 |issue= 2 |pages= 313–25 |year= 2000 |pmid= 10985351 |doi=10.1016/S0896-6273(00)00039-8  |s2cid=16213962 |doi-access=free }}
*{{cite journal   |vauthors=Chung HJ, Xia J, Scannevin RH, etal |title=Phosphorylation of the AMPA receptor subunit GluR2 differentially regulates its interaction with PDZ domain-containing proteins. |journal=J. Neurosci. |volume=20 |issue= 19 |pages= 7258–67 |year= 2001 |pmid= 11007883 |pmc=6772789 |doi=  10.1523/JNEUROSCI.20-19-07258.2000}}
*{{cite journal  |vauthors=Armstrong N, Gouaux E |title=Mechanisms for activation and antagonism of an AMPA-sensitive glutamate receptor: crystal structures of the GluR2 ligand binding core. |journal=Neuron |volume=28 |issue= 1 |pages= 165–81 |year= 2000 |pmid= 11086992 |doi=10.1016/S0896-6273(00)00094-5  |s2cid=3128719 |doi-access=free }}
*{{cite journal   |vauthors=Krampfl K, Schlesinger F, Zörner A, etal |title=Control of kinetic properties of GluR2 flop AMPA-type channels: impact of R/G nuclear editing. |journal=Eur. J. Neurosci. |volume=15 |issue= 1 |pages= 51–62 |year= 2002 |pmid= 11860506 |doi=10.1046/j.0953-816x.2001.01841.x  |s2cid=35601416 }}
*{{cite journal   |vauthors=Hirbec H, Perestenko O, Nishimune A, etal |title=The PDZ proteins PICK1, GRIP, and syntenin bind multiple glutamate receptor subtypes. Analysis of PDZ binding motifs. |journal=J. Biol. Chem. |volume=277 |issue= 18 |pages= 15221–4 |year= 2002 |pmid= 11891216 |doi= 10.1074/jbc.C200112200 |doi-access= free |hdl= 2262/89271 |hdl-access= free }}
{{refend}}
== External links ==
* {{MeshName|GRIA2+protein,+human}}
* http://darned.ucc.ie
{{NLM content}}
{{PDB Gallery|geneid=2891}}
{{Ligand-gated ion channels}}
{{DEFAULTSORT:Gria2}}
[[Category:Ionotropic glutamate receptors]]