Identification and characterization of a novel phosphorylation site on the GluR1 subunit of AMPA receptors.
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.
Lee
Hey-Kyoung
HK
Howard Hughes Medical Institute, Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. hlee21@umd.edu
Takamiya
Kogo
K
Kameyama
Kimihiko
K
He
Kaiwen
K
Yu
Sandy
S
Rossetti
Luciano
L
Wilen
David
D
Huganir
Richard L
RL
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
D011493:Protein Kinase C; D018091:Receptors, AMPA; D013912:Threonine
J Neurosci. 2000 Jan 1;20(1):89-102
10627585
J Neurochem. 1999 Oct;73(4):1765-8
10501226
J Neurosci. 2005 Mar 16;25(11):2992-3001
15772359
Neuron. 2006 Jul 20;51(2):213-25
16846856
EMBO J. 2000 Jun 15;19(12):2765-74
10856222
Nature. 2000 Jun 22;405(6789):955-9
10879537
J Neurosci. 2000 Oct 1;20(19):7258-67
11007883
Neuron. 2000 Nov;28(2):499-510
11144359
Neuron. 2000 Dec;28(3):873-86
11163273
Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11725-30
11573007
Trends Neurosci. 2002 Nov;25(11):578-88
12392933
Nat Neurosci. 2003 Jan;6(1):15-6
12469130
Nat Neurosci. 2003 Feb;6(2):136-43
12536214
Cell. 2003 Mar 7;112(5):631-43
12628184
Science. 2003 Jun 13;300(5626):1751-5
12805550
Neuropharmacology. 2003 Nov;45(6):828-36
14529720
J Neurosci. 2003 Oct 8;23(27):9220-8
14534256
J Physiol. 2003 Dec 15;553(Pt 3):843-56
14555717
J Neurosci. 2004 May 26;24(21):4903-11
15163681
Brain Res. 1986 Mar 19;368(2):347-50
3697730
Proc Natl Acad Sci U S A. 1992 May 15;89(10):4363-7
1350090
J Neurosci. 1994 Dec;14(12):7585-93
7527845
Neuron. 1996 Jun;16(6):1179-88
8663994
Science. 1997 Jun 27;276(5321):2042-5
9197267
J Biol Chem. 1997 Dec 19;272(51):32528-33
9405465
J Biol Chem. 1997 Dec 26;272(52):32727-30
9407043
Curr Biol. 1998 May 21;8(11):661-4
9635194
Neuron. 1998 Nov;21(5):1151-62
9856470
Neuron. 1998 Nov;21(5):1163-75
9856471
Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3269-74
10077673
Science. 1999 Jun 11;284(5421):1805-11
10364547
J Neurosci. 1999 Jun 15;19(12):4748-54
10366608
Nat Rev Neurosci. 2004 Dec;5(12):952-62
15550950