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

J. Neurosci. 23 (7): 2634-2644

Copyright © 2003 by the Society for Neuroscience.

The Journal of Neuroscience, April 1, 2003, 23(7):2634

Derangements of Hippocampal Calcium/Calmodulin-Dependent Protein Kinase II in a Mouse Model for Angelman Mental Retardation Syndrome

Edwin J. Weeber1, Yong-Hui Jiang2, Ype Elgersma3, 4, Andrew W. Varga1, Yarimar Carrasquillo1, Sarah E. Brown1, Jill M. Christian1, Banefsheh Mirnikjoo1, Alcino Silva3, Arthur L. Beaudet2, and J. David Sweatt1

1 Division of Neuroscience and 2 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, 3 Department of Neurobiology, University of California, Los Angeles, Medical Center, Los Angeles, California 90095-1763, and 4 Department of Neuroscience, Erasmus University Rotterdam, 3000 DR Rotterdam, The Netherlands

Angelman syndrome (AS) is a disorder of human cognition characterized by severe mental retardation and epilepsy. Recently, a mouse model for AS (Ube3a maternal null mutation) was developed that displays deficits in both context-dependent learning and hippocampal long-term potentiation (LTP). In the present studies, we examined the molecular basis for these LTP and learning deficits. Mutant animals exhibited a significant increase in hippocampal phospho-calcium/calmodulin-dependent protein kinase II (CaMKII), specifically at sites Thr286 and Thr305, with no corresponding change in the levels of total CaMKII. In addition, mutants show a reduction in CaMKII activity, autophosphorylation capability, and total CaMKII associated with postsynaptic density. These findings are the first to implicate misregulation of CaMKII as a molecular cause for the neurobehavioral deficits in a human learning disorder.

Key words: Angelman syndrome; calcium/calmodulin-dependent protein kinase II; long-term potentiation; postsynaptic density; protein phosphatase; autophosphorylation

Copyright © 2003 Society for Neuroscience  0270-6474/03/2372634-11$05.00/0

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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 »
Decreased Tonic Inhibition in Cerebellar Granule Cells Causes Motor Dysfunction in a Mouse Model of Angelman Syndrome.
K. Egawa, K. Kitagawa, K. Inoue, M. Takayama, C. Takayama, S. Saitoh, T. Kishino, M. Kitagawa, and A. Fukuda (2012)
Science Translational Medicine 4, 163ra157
   Abstract »    Full Text »    PDF »
Activity-Dependent Modulation of the Interaction between CaMKII{alpha} and Abi1 and Its Involvement in Spine Maturation.
E. Park, S. Chi, and D. Park (2012)
J. Neurosci. 32, 13177-13188
   Abstract »    Full Text »    PDF »
Ca2+/Calmodulin-dependent Protein Kinase II{alpha} ({alpha}CaMKII) Controls the Activity of the Dopamine Transporter: IMPLICATIONS FOR ANGELMAN SYNDROME.
T. Steinkellner, J.-W. Yang, T. R. Montgomery, W.-Q. Chen, M.-T. Winkler, S. Sucic, G. Lubec, M. Freissmuth, Y. Elgersma, H. H. Sitte, et al. (2012)
J. Biol. Chem. 287, 29627-29635
   Abstract »    Full Text »    PDF »
Defective glucocorticoid hormone receptor signaling leads to increased stress and anxiety in a mouse model of Angelman syndrome.
S. K. Godavarthi, P. Dey, M. Maheshwari, and N. Ranjan Jana (2012)
Hum. Mol. Genet. 21, 1824-1834
   Abstract »    Full Text »    PDF »
Alterations in Intrinsic Membrane Properties and the Axon Initial Segment in a Mouse Model of Angelman Syndrome.
H. Kaphzan, S. A. Buffington, J. I. Jung, M. N. Rasband, and E. Klann (2011)
J. Neurosci. 31, 17637-17648
   Abstract »    Full Text »    PDF »
Increased Gene Dosage of Ube3a Results in Autism Traits and Decreased Glutamate Synaptic Transmission in Mice.
S. E. P. Smith, Y.-D. Zhou, G. Zhang, Z. Jin, D. C. Stoppel, and M. P. Anderson (2011)
Science Translational Medicine 3, 103ra97
   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 »
Aberrant Calcium/Calmodulin-Dependent Protein Kinase II (CaMKII) Activity Is Associated with Abnormal Dendritic Spine Morphology in the ATRX Mutant Mouse Brain.
N. Shioda, H. Beppu, T. Fukuda, E. Li, I. Kitajima, and K. Fukunaga (2011)
J. Neurosci. 31, 346-358
   Abstract »    Full Text »    PDF »
Angelman Syndrome, a Genomic Imprinting Disorder of the Brain.
S. J. Chamberlain and M. Lalande (2010)
J. Neurosci. 30, 9958-9963
   Full Text »    PDF »
Autonomous CaMKII Can Promote either Long-Term Potentiation or Long-Term Depression, Depending on the State of T305/T306 Phosphorylation.
H. J. Pi, N. Otmakhov, D. Lemelin, P. De Koninck, and J. Lisman (2010)
J. Neurosci. 30, 8704-8709
   Abstract »    Full Text »    PDF »
Genomic imprinting of experience-dependent cortical plasticity by the ubiquitin ligase gene Ube3a.
M. Sato and M. P. Stryker (2010)
PNAS 107, 5611-5616
   Abstract »    Full Text »    PDF »
Domoic Acid Induces a Long-Lasting Enhancement of CA1 Field Responses and Impairs Tetanus-Induced Long-term Potentiation in Rat Hippocampal Slices.
S. Qiu, A. K. Jebelli, J. H. Ashe, and M. C. Curras-Collazo (2009)
Toxicol. Sci. 111, 140-150
   Abstract »    Full Text »    PDF »
CaMKII phosphorylation of the GABAA receptor: receptor subtype- and synapse-specific modulation.
C. M. Houston, Q. He, and T. G. Smart (2009)
J. Physiol. 587, 2115-2125
   Abstract »    Full Text »    PDF »
Neuronal Death Resulting from Targeted Disruption of the Snf2 Protein ATRX Is Mediated by p53.
C. Seah, M. A. Levy, Y. Jiang, S. Mokhtarzada, D. R. Higgs, R. J. Gibbons, and N. G. Berube (2008)
J. Neurosci. 28, 12570-12580
   Abstract »    Full Text »    PDF »
Distinct Regulation of {beta}2 and {beta}3 Subunit-Containing Cerebellar Synaptic GABAA Receptors by Calcium/Calmodulin-Dependent Protein Kinase II.
C. M. Houston, A. M. Hosie, and T. G. Smart (2008)
J. Neurosci. 28, 7574-7584
   Abstract »    Full Text »    PDF »
Association of Protein Phosphatase 1{gamma}1 with Spinophilin Suppresses Phosphatase Activity in a Parkinson Disease Model.
A. M. Brown, A. J. Baucum, M. A. Bass, and R. J. Colbran (2008)
J. Biol. Chem. 283, 14286-14294
   Abstract »    Full Text »    PDF »
The Angelman syndrome ubiquitin ligase localizes to the synapse and nucleus, and maternal deficiency results in abnormal dendritic spine morphology.
S. V. Dindot, B. A. Antalffy, M. B. Bhattacharjee, and A. L. Beaudet (2008)
Hum. Mol. Genet. 17, 111-118
   Abstract »    Full Text »    PDF »
Emerging Roles for Ubiquitin and Protein Degradation in Neuronal Function.
J. J. Yi and M. D. Ehlers (2007)
Pharmacol. Rev. 59, 14-39
   Abstract »    Full Text »    PDF »
Enriching the environment of {alpha}CaMKIIT286A mutant mice reveals that LTD occurs in memory processing but must be subsequently reversed by LTP.
S. L. Parsley, S. M. Pilgram, F. Soto, K. P. Giese, and F. A. Edwards (2007)
Learn. Mem. 14, 75-83
   Abstract »    Full Text »    PDF »
Differential Modulation of Ca2+/Calmodulin-dependent Protein Kinase II Activity by Regulated Interactions with N-Methyl-D-aspartate Receptor NR2B Subunits and {alpha}-Actinin.
A. J. Robison, R. K. Bartlett, M. A. Bass, and R. J. Colbran (2005)
J. Biol. Chem. 280, 39316-39323
   Abstract »    Full Text »    PDF »
Maternal disruption of Ube3a leads to increased expression of Ube3a-ATS in trans.
M. Landers, M. A. Calciano, D. Colosi, H. Glatt-Deeley, J. Wagstaff, and M. Lalande (2005)
Nucleic Acids Res. 33, 3976-3984
   Abstract »    Full Text »    PDF »
Interaction between Dinucleotide and Nicotinic Receptors in Individual Cholinergic Terminals.
M. Diaz-Hernandez, J. Sanchez-Nogueiro, J. Pintor, and M. T. Miras-Portugal (2004)
J. Pharmacol. Exp. Ther. 311, 954-967
   Abstract »    Full Text »    PDF »
Activity-Dependent Regulation of Calcium/Calmodulin-Dependent Protein Kinase II Localization.
H. Schulman (2004)
J. Neurosci. 24, 8399-8403
   Full Text »    PDF »
Protein Phosphatases and Calcium/Calmodulin-Dependent Protein Kinase II-Dependent Synaptic Plasticity.
R. J. Colbran (2004)
J. Neurosci. 24, 8404-8409
   Full Text »    PDF »
Mouse Genetic Approaches to Investigating Calcium/Calmodulin-Dependent Protein Kinase II Function in Plasticity and Cognition.
Y. Elgersma, J. D. Sweatt, and K. P. Giese (2004)
J. Neurosci. 24, 8410-8415
   Full Text »    PDF »

To Advertise     Find Products

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