title: Identification and characterization of a novel phosphorylation site on the GluR1 subunit of AMPA receptors.
abstract: Phosphorylation of various AMPA receptor subunits can alter synaptic transmission and plasticity at excitatory glutamatergic synapses in the central nervous system. Here, we identified threonine-840 (T840) on the GluR1 subunit of AMPA receptors as a novel phosphorylation site. T840 is phosphorylated by protein kinase C (PKC) in vitro and is a highly turned-over phosphorylation site in the hippocampus. Interestingly, the high basal phosphorylation of T840 in the hippocampus is maintained by a persistent activity of a protein kinase, which is counter-balanced by a basal protein phosphatase activity. To study the function of T840, we generated a line of mutant mice lacking this phosphorylation site using a gene knock-in technique. The mice generated lack T840, in addition to two previously identified phosphorylation sites S831 and S845. Using this mouse, we demonstrate that T840 may regulate synaptic plasticity in an age-dependent manner.
authors: Howard Hughes Medical Institute, Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. hlee21@umd.edu
authors: Hey-Kyoung
authors: HK
authors: Lee
authors: Kogo
authors: K
authors: Takamiya
authors: Kimihiko
authors: K
authors: Kameyama
authors: Kaiwen
authors: K
authors: He
authors: Sandy
authors: S
authors: Yu
authors: Luciano
authors: L
authors: Rossetti
authors: David
authors: D
authors: Wilen
authors: Richard L
authors: RL
authors: Huganir
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D013912:Threonine / Q000378:metabolism*; D014162:Transfection / Q000379:methods
chemical_list: D011493:Protein Kinase C; D018091:Receptors, AMPA; D013912:Threonine
references: J Neurosci. 2000 Jan 1;20(1):89-102
references: 10627585
references: J Neurochem. 1999 Oct;73(4):1765-8
references: 10501226
references: J Neurosci. 2005 Mar 16;25(11):2992-3001
references: 15772359
references: Neuron. 2006 Jul 20;51(2):213-25
references: 16846856
references: EMBO J. 2000 Jun 15;19(12):2765-74
references: 10856222
references: Nature. 2000 Jun 22;405(6789):955-9
references: 10879537
references: J Neurosci. 2000 Oct 1;20(19):7258-67
references: 11007883
references: Neuron. 2000 Nov;28(2):499-510
references: 11144359
references: Neuron. 2000 Dec;28(3):873-86
references: 11163273
references: Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11725-30
references: 11573007
references: Trends Neurosci. 2002 Nov;25(11):578-88
references: 12392933
references: Nat Neurosci. 2003 Jan;6(1):15-6
references: 12469130
references: Nat Neurosci. 2003 Feb;6(2):136-43
references: 12536214
references: Cell. 2003 Mar 7;112(5):631-43
references: 12628184
references: Science. 2003 Jun 13;300(5626):1751-5
references: 12805550
references: Neuropharmacology. 2003 Nov;45(6):828-36
references: 14529720
references: J Neurosci. 2003 Oct 8;23(27):9220-8
references: 14534256
references: J Physiol. 2003 Dec 15;553(Pt 3):843-56
references: 14555717
references: J Neurosci. 2004 May 26;24(21):4903-11
references: 15163681
references: Brain Res. 1986 Mar 19;368(2):347-50
references: 3697730
references: Proc Natl Acad Sci U S A. 1992 May 15;89(10):4363-7
references: 1350090
references: J Neurosci. 1994 Dec;14(12):7585-93
references: 7527845
references: Neuron. 1996 Jun;16(6):1179-88
references: 8663994
references: Science. 1997 Jun 27;276(5321):2042-5
references: 9197267
references: J Biol Chem. 1997 Dec 19;272(51):32528-33
references: 9405465
references: J Biol Chem. 1997 Dec 26;272(52):32727-30
references: 9407043
references: Curr Biol. 1998 May 21;8(11):661-4
references: 9635194
references: Neuron. 1998 Nov;21(5):1151-62
references: 9856470
references: Neuron. 1998 Nov;21(5):1163-75
references: 9856471
references: Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3269-74
references: 10077673
references: Science. 1999 Jun 11;284(5421):1805-11
references: 10364547
references: J Neurosci. 1999 Jun 15;19(12):4748-54
references: 10366608
references: Nat Rev Neurosci. 2004 Dec;5(12):952-62
references: 15550950