Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Science 300 (5626): 1751-1755

Copyright © 2003 by the American Association for the Advancement of Science

Requirement of AMPA Receptor GluR2 Phosphorylation for Cerebellar Long-Term Depression

Hee Jung Chung,1,2* Jordan P. Steinberg,1,2* Richard L. Huganir,1,2 David J. Linden2{dagger}

Abstract: Cerebellar long-term depression (LTD) is a model of synaptic memory that requires protein kinase C (PKC) activation and is expressed as a reduction in the number of postsynaptic {alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors. LTD was absent in cultured cerebellar Purkinje cells from mutant mice lacking the AMPA receptor GluR2 subunit and could be rescued by transient transfection with the wild-type GluR2 subunit. Transfection with a point mutant that eliminated PKC phosphorylation of Ser880 in the carboxy-terminal PDZ ligand of GluR2 failed to restore LTD. In contrast, transfection with a point mutant that mimicked phosphorylation at Ser880 occluded subsequent LTD. Thus, PKC phosphorylation of GluR2 Ser880 is a critical event in the induction of cerebellar LTD.

1 Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205 USA.
2 Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205 USA.

Back to Top

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: dlinden{at}jhmi.edu

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Synaptic and Intrinsic Homeostatic Mechanisms Cooperate to Increase L2/3 Pyramidal Neuron Excitability during a Late Phase of Critical Period Plasticity.
M. E. Lambo and G. G. Turrigiano (2013)
J. Neurosci. 33, 8810-8819
   Abstract »    Full Text »    PDF »
Gating of long-term depression by Ca2+/calmodulin-dependent protein kinase II through enhanced cGMP signalling in cerebellar Purkinje cells.
S.-y. Kawaguchi and T. Hirano (2013)
J. Physiol. 591, 1707-1730
   Abstract »    Full Text »    PDF »
The {delta}2 glutamate receptor gates long-term depression by coordinating interactions between two AMPA receptor phosphorylation sites.
K. Kohda, W. Kakegawa, S. Matsuda, T. Yamamoto, H. Hirano, and M. Yuzaki (2013)
PNAS 110, E948-E957
   Abstract »    Full Text »    PDF »
Raf Kinase Inhibitory Protein is Required for Cerebellar Long-Term Synaptic Depression by Mediating PKC-Dependent MAPK Activation.
Y. Yamamoto, D. Lee, Y. Kim, B. Lee, C. Seo, H. Kawasaki, S. Kuroda, and K. Tanaka-Yamamoto (2012)
J. Neurosci. 32, 14254-14264
   Abstract »    Full Text »    PDF »
Transient Receptor Potential Canonical Channels Regulate the Induction of Cerebellar Long-Term Depression.
H. G. Chae, S. J. Ahn, Y. H. Hong, W. S. Chang, J. Kim, and S. J. Kim (2012)
J. Neurosci. 32, 12909-12914
   Abstract »    Full Text »    PDF »
Proteomic Analysis of {alpha}-Amino-3-hydroxy-5-methyl-4-isoxazole Propionate Receptor Complexes.
M.-G. Kang, M. Nuriya, Y. Guo, K. D. Martindale, D. Z. Lee, and R. L. Huganir (2012)
J. Biol. Chem. 287, 28632-28645
   Abstract »    Full Text »    PDF »
A Stochastic Signaling Network Mediates the Probabilistic Induction of Cerebellar Long-Term Depression.
G. Antunes and E. De Schutter (2012)
J. Neurosci. 32, 9288-9300
   Abstract »    Full Text »    PDF »
Estimating abundances of retroviral insertion sites from DNA fragment length data.
C. C. Berry, N. A. Gillet, A. Melamed, N. Gormley, C. R. M. Bangham, and F. D. Bushman (2012)
Bioinformatics 28, 755-762
   Abstract »    Full Text »    PDF »
Lack of Kinase Regulation of Canonical Transient Receptor Potential 3 (TRPC3) Channel-dependent Currents in Cerebellar Purkinje Cells.
C. Nelson and M. D. Glitsch (2012)
J. Biol. Chem. 287, 6326-6335
   Abstract »    Full Text »    PDF »
A late phase of LTD in cultured cerebellar Purkinje cells requires persistent dynamin-mediated endocytosis.
D. J. Linden (2012)
J Neurophysiol 107, 448-454
   Abstract »    Full Text »    PDF »
Adenylate cyclase 1 promotes strengthening and experience-dependent plasticity of whisker relay synapses in the thalamus.
H. Wang, H. Liu, D. R. Storm, and Z.-w. Zhang (2011)
J. Physiol. 589, 5649-5662
   Abstract »    Full Text »    PDF »
Mutant PKC{gamma} in Spinocerebellar Ataxia Type 14 Disrupts Synapse Elimination and Long-Term Depression in Purkinje Cells In Vivo.
A. N. Shuvaev, H. Horiuchi, T. Seki, H. Goenawan, T. Irie, A. Iizuka, N. Sakai, and H. Hirai (2011)
J. Neurosci. 31, 14324-14334
   Abstract »    Full Text »    PDF »
Impaired Locomotor Learning and Altered Cerebellar Synaptic Plasticity in pep-19/pcp4-Null Mice.
P. Wei, J. A. Blundon, Y. Rong, S. S. Zakharenko, and J. I. Morgan (2011)
Mol. Cell. Biol. 31, 2838-2844
   Abstract »    Full Text »    PDF »
Excitatory synaptic transmission and network activity are depressed following mechanical injury in cortical neurons.
P. B. Goforth, J. Ren, B. S. Schwartz, and L. S. Satin (2011)
J Neurophysiol 105, 2350-2363
   Abstract »    Full Text »    PDF »
Removal of Synaptic Ca2+-Permeable AMPA Receptors during Sleep.
F. Lante, J.-C. Toledo-Salas, T. Ondrejcak, M. J. Rowan, and D. Ulrich (2011)
J. Neurosci. 31, 3953-3961
   Abstract »    Full Text »    PDF »
Ras and Rap Signaling in Synaptic Plasticity and Mental Disorders.
R. L. Stornetta and J. J. Zhu (2011)
Neuroscientist 17, 54-78
   Abstract »    PDF »
Calcium Binding to PICK1 Is Essential for the Intracellular Retention of AMPA Receptors Underlying Long-Term Depression.
A. Citri, S. Bhattacharyya, C. Ma, W. Morishita, S. Fang, J. Rizo, and R. C. Malenka (2010)
J. Neurosci. 30, 16437-16452
   Abstract »    Full Text »    PDF »
GRIP1 and 2 regulate activity-dependent AMPA receptor recycling via exocyst complex interactions.
L. Mao, K. Takamiya, G. Thomas, D.-T. Lin, and R. L. Huganir (2010)
PNAS 107, 19038-19043
   Abstract »    Full Text »    PDF »
Phosphorylation-State-Dependent Regulation of NMDA Receptor Short-Term Plasticity Modifies Hippocampal Dendritic Ca2+ Transients.
D. Chatterjea, E. Hamid, J. P. Leonard, and S. Alford (2010)
J Neurophysiol 104, 2203-2213
   Abstract »    Full Text »    PDF »
Dendritic Kv3.3 Potassium Channels in Cerebellar Purkinje Cells Regulate Generation and Spatial Dynamics of Dendritic Ca2+ Spikes.
E. Zagha, S. Manita, W. N. Ross, and B. Rudy (2010)
J Neurophysiol 103, 3516-3525
   Abstract »    Full Text »    PDF »
AMPA receptor subunits define properties of state-dependent synaptic plasticity.
M. R. Emond, J. M. Montgomery, M. L. Huggins, J. E. Hanson, L. Mao, R. L. Huganir, and D. V. Madison (2010)
J. Physiol. 588, 1929-1946
   Abstract »    Full Text »    PDF »
Increased Insertion of Glutamate Receptor 2-Lacking {alpha}-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid (AMPA) Receptors at Hippocampal Synapses upon Repeated Morphine Administration.
S. K. Billa, J. Liu, N. L. Bjorklund, N. Sinha, Y. Fu, P. Shinnick-Gallagher, and J. A. Moron (2010)
Mol. Pharmacol. 77, 874-883
   Abstract »    Full Text »    PDF »
Presynaptic m1 muscarinic receptors are necessary for mGluR long-term depression in the hippocampus.
A. Kamsler, T. J. McHugh, D. Gerber, S. Y. Huang, and S. Tonegawa (2010)
PNAS 107, 1618-1623
   Abstract »    Full Text »    PDF »
Specific Roles of AMPA Receptor Subunit GluR1 (GluA1) Phosphorylation Sites in Regulating Synaptic Plasticity in the CA1 Region of Hippocampus.
H.-K. Lee, K. Takamiya, K. He, L. Song, and R. L. Huganir (2010)
J Neurophysiol 103, 479-489
   Abstract »    Full Text »    PDF »
HNK-1 Glyco-epitope Regulates the Stability of the Glutamate Receptor Subunit GluR2 on the Neuronal Cell Surface.
I. Morita, S. Kakuda, Y. Takeuchi, S. Itoh, N. Kawasaki, Y. Kizuka, T. Kawasaki, and S. Oka (2009)
J. Biol. Chem. 284, 30209-30217
   Abstract »    Full Text »    PDF »
Role of Presynaptic Kainate Receptors at Parallel Fiber-Purkinje Cell Synapses in Induction of Cerebellar LTD: Interplay With Climbing Fiber Input.
F. Crepel (2009)
J Neurophysiol 102, 965-973
   Abstract »    Full Text »    PDF »
Synaptic Scaling Requires the GluR2 Subunit of the AMPA Receptor.
M. A. Gainey, J. R. Hurvitz-Wolff, M. E. Lambo, and G. G. Turrigiano (2009)
J. Neurosci. 29, 6479-6489
   Abstract »    Full Text »    PDF »
Persistent Inflammation Induces GluR2 Internalization via NMDA Receptor-Triggered PKC Activation in Dorsal Horn Neurons.
J.-S. Park, N. Voitenko, R. S. Petralia, X. Guan, J.-T. Xu, J. P. Steinberg, K. Takamiya, A. Sotnik, O. Kopach, R. L. Huganir, et al. (2009)
J. Neurosci. 29, 3206-3219
   Abstract »    Full Text »    PDF »
Cytosolic PLA2{alpha} activation in Purkinje neurons and its role in AMPA-receptor trafficking.
M. Mashimo, T. Hirabayashi, T. Murayama, and T. Shimizu (2008)
J. Cell Sci. 121, 3015-3024
   Abstract »    Full Text »    PDF »
AKAP150-anchored PKA activity is important for LTD during its induction phase.
Y. Lu, M. Zhang, I. A. Lim, D. D. Hall, M. Allen, Y. Medvedeva, G. S. McKnight, Y. M. Usachev, and J. W. Hell (2008)
J. Physiol. 586, 4155-4164
   Abstract »    Full Text »    PDF »
The Glutamate Receptor-Interacting Protein Family of GluR2-Binding Proteins Is Required for Long-Term Synaptic Depression Expression in Cerebellar Purkinje Cells.
K. Takamiya, L. Mao, R. L. Huganir, and D. J. Linden (2008)
J. Neurosci. 28, 5752-5755
   Abstract »    Full Text »    PDF »
Endocytosis and recycling of AMPA receptors lacking GluR2/3.
V. Biou, S. Bhattacharyya, and R. C. Malenka (2008)
PNAS 105, 1038-1043
   Abstract »    Full Text »    PDF »
PICK1 and Phosphorylation of the Glutamate Receptor 2 (GluR2) AMPA Receptor Subunit Regulates GluR2 Recycling after NMDA Receptor-Induced Internalization.
D.-T. Lin and R. L. Huganir (2007)
J. Neurosci. 27, 13903-13908
   Abstract »    Full Text »    PDF »
Postsynaptic GABAB receptor signalling enhances LTD in mouse cerebellar Purkinje cells.
Y. Kamikubo, T. Tabata, S. Kakizawa, D. Kawakami, M. Watanabe, A. Ogura, M. Iino, and M. Kano (2007)
J. Physiol. 585, 549-563
   Abstract »    Full Text »    PDF »
Long-Term Modifications in the Strength of Excitatory Associative Inputs in the Piriform Cortex.
A. Young and Q.-Q. Sun (2007)
Chem Senses 32, 783-794
   Abstract »    Full Text »    PDF »
Activation of extrasynaptic NMDA receptors induces a PKC-dependent switch in AMPA receptor subtypes in mouse cerebellar stellate cells.
L. Sun and S. June Liu (2007)
J. Physiol. 583, 537-553
   Abstract »    Full Text »    PDF »
PKC and polyamine modulation of GluR2-deficient AMPA receptors in immature neocortical pyramidal neurons of the rat.
J. Shin, F. Shen, and J. Huguenard (2007)
J. Physiol. 581, 679-691
   Abstract »    Full Text »    PDF »
Differential Regulation of AMPA Receptor Trafficking by Neurabin-Targeted Synaptic Protein Phosphatase-1 in Synaptic Transmission and Long-Term Depression in Hippocampus.
X.-d. Hu, Q. Huang, X. Yang, and H. Xia (2007)
J. Neurosci. 27, 4674-4686
   Abstract »    Full Text »    PDF »
Isoform specificity of protein kinase Cs in synaptic plasticity.
W. S. Sossin (2007)
Learn. Mem. 14, 236-246
   Abstract »    Full Text »    PDF »
Phosphorylation of Glutamate Receptor Interacting Protein 1 Regulates Surface Expression of Glutamate Receptors.
K. Kulangara, M. Kropf, L. Glauser, S. Magnin, S. Alberi, A. Yersin, and H. Hirling (2007)
J. Biol. Chem. 282, 2395-2404
   Abstract »    Full Text »    PDF »
Casein kinase 2-dependent serine phosphorylation of MuSK regulates acetylcholine receptor aggregation at the neuromuscular junction..
T. Cheusova, M. A. Khan, S. W. Schubert, A.-C. Gavin, T. Buchou, G. Jacob, H. Sticht, J. Allende, B. Boldyreff, H. R. Brenner, et al. (2006)
Genes & Dev. 20, 1800-1816
   Abstract »    Full Text »    PDF »
Involvement of basal protein kinase C and extracellular signal-regulated kinase 1/2 activities in constitutive internalization of AMPA receptors in cerebellar Purkinje cells..
T. Tatsukawa, T. Chimura, H. Miyakawa, and K. Yamaguchi (2006)
J. Neurosci. 26, 4820-4825
   Abstract »    Full Text »    PDF »
Membrane-proximal region of glutamate receptor delta2 subunit is critical for long-term depression and interaction with protein interacting with C kinase 1 in a cerebellar Purkinje neuron..
S. Yawata, H. Tsuchida, M. Kengaku, and T. Hirano (2006)
J. Neurosci. 26, 3626-3633
   Abstract »    Full Text »    PDF »
Auxiliary Subunits Assist AMPA-Type Glutamate Receptors..
R. A. Nicoll, S. Tomita, and D. S. Bredt (2006)
Science 311, 1253-1256
   Abstract »    Full Text »    PDF »
Function of cGMP-Dependent Protein Kinases as Revealed by Gene Deletion.
F. Hofmann, R. Feil, T. Kleppisch, and J. Schlossmann (2006)
Physiol Rev 86, 1-23
   Abstract »    Full Text »    PDF »
When the B-team runs plasticity: GluR2 receptor trafficking in cerebellar long-term potentiation.
C. Hansel (2005)
PNAS 102, 18245-18246
   Full Text »    PDF »
An NMDA Receptor/Nitric Oxide Cascade Is Involved in Cerebellar LTD But Is Not Localized to the Parallel Fiber Terminal.
J. H. Shin and D. J. Linden (2005)
J Neurophysiol 94, 4281-4289
   Abstract »    Full Text »    PDF »
A Role for Protein Phosphatases 1, 2A, and 2B in Cerebellar Long-Term Potentiation.
A. Belmeguenai and C. Hansel (2005)
J. Neurosci. 25, 10768-10772
   Abstract »    Full Text »    PDF »
Phospholipase C{delta}4 Associates with Glutamate Receptor Interacting Protein 1 in Testis.
Y. Irino, M. Ichinohe, Y. Nakamura, M. Nakahara, and K. Fukami (2005)
J. Biochem. 138, 451-456
   Abstract »    Full Text »    PDF »
Spines and neurite branches function as geometric attractors that enhance protein kinase C action.
M. L. Craske, M. Fivaz, N. N. Batada, and T. Meyer (2005)
J. Cell Biol. 170, 1147-1158
   Abstract »    Full Text »    PDF »
Genetic Enhancement of Visual Learning by Activation of Protein Kinase C Pathways in Small Groups of Rat Cortical Neurons.
G.-r. Zhang, X. Wang, L. Kong, X.-g. Lu, B. Lee, M. Liu, M. Sun, C. Franklin, R. G. Cook, and A. I. Geller (2005)
J. Neurosci. 25, 8468-8481
   Abstract »    Full Text »    PDF »
Desensitization of canonical transient receptor potential channel 5 by protein kinase C.
M. H. Zhu, M. Chae, H. J. Kim, Y. M. Lee, M. J. Kim, N. G. Jin, D. K. Yang, I. So, and K. W. Kim (2005)
Am J Physiol Cell Physiol 289, C591-C600
   Abstract »    Full Text »    PDF »
The Molecular Pharmacology and Cell Biology of {alpha}-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptors.
C. L. Palmer, L. Cotton, and J. M. Henley (2005)
Pharmacol. Rev. 57, 253-277
   Abstract »    Full Text »    PDF »
Polyamines Modulate AMPA Receptor-Dependent Synaptic Responses in Immature Layer V Pyramidal Neurons.
J. Shin, F. Shen, and J. R. Huguenard (2005)
J Neurophysiol 93, 2634-2643
   Abstract »    Full Text »    PDF »
Protein kinase C gamma mutations in spinocerebellar ataxia 14 increase kinase activity and alter membrane targeting.
D. S. Verbeek, M. A. Knight, G. G. Harmison, K. H. Fischbeck, and B. W. Howell (2005)
Brain 128, 436-442
   Abstract »    Full Text »    PDF »
N-ethylmaleimide-sensitive factor is required for the synaptic incorporation and removal of AMPA receptors during cerebellar long-term depression.
J. P. Steinberg, R. L. Huganir, and D. J. Linden (2004)
PNAS 101, 18212-18216
   Abstract »    Full Text »    PDF »
Regulation of the NMDA Receptor Complex and Trafficking by Activity-Dependent Phosphorylation of the NR2B Subunit PDZ Ligand.
H. J. Chung, Y. H. Huang, L.-F. Lau, and R. L. Huganir (2004)
J. Neurosci. 24, 10248-10259
   Abstract »    Full Text »    PDF »
Tyrosine Phosphorylation and Regulation of the AMPA Receptor by Src Family Tyrosine Kinases.
T. Hayashi and R. L. Huganir (2004)
J. Neurosci. 24, 6152-6160
   Abstract »    Full Text »    PDF »
Dynamic Interaction of Stargazin-like TARPs with Cycling AMPA Receptors at Synapses.
S. Tomita, M. Fukata, R. A. Nicoll, and D. S. Bredt (2004)
Science 303, 1508-1511
   Abstract »    Full Text »    PDF »
Protein phosphatase 2A inhibition induces cerebellar long-term depression and declustering of synaptic AMPA receptor.
T. Launey, S. Endo, R. Sakai, J. Harano, and M. Ito (2004)
PNAS 101, 676-681
   Abstract »    Full Text »    PDF »
Impairment of LTD and cerebellar learning by Purkinje cell-specific ablation of cGMP-dependent protein kinase I.
R. Feil, J. Hartmann, C. Luo, W. Wolfsgruber, K. Schilling, S. Feil, J. J. Barski, M. Meyer, A. Konnerth, C. I. De Zeeuw, et al. (2003)
J. Cell Biol. 163, 295-302
   Abstract »    Full Text »    PDF »
Glutamate Receptor Subunit 2 Serine 880 Phosphorylation Modulates Synaptic Transmission and Mediates Plasticity in CA1 Pyramidal Cells.
K. J. Seidenman, J. P. Steinberg, R. Huganir, and R. Malinow (2003)
J. Neurosci. 23, 9220-9228
   Abstract »    Full Text »    PDF »
NEUROSCIENCE: From Molecules to Memory in the Cerebellum.
D. J. Linden (2003)
Science 301, 1682-1685
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882