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Science 2 July 1999:
Vol. 285. no. 5424, pp. 93 - 96
DOI: 10.1126/science.285.5424.93
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Regulation of NMDA Receptors by an Associated Phosphatase-Kinase Signaling Complex

Ryan S. Westphal, 1* Steven J. Tavalin, 1* Jerry W. Lin, 2 Neal M. Alto, 1 Iain D. C. Fraser, 1 Lorene K. Langeberg, 1 Morgan Sheng, 2 John D. Scott 1dagger

Regulation of N-methyl-D-aspartate (NMDA) receptor activity by kinases and phosphatases contributes to the modulation of synaptic transmission. Targeting of these enzymes near the substrate is proposed to enhance phosphorylation-dependent modulation. Yotiao, an NMDA receptor-associated protein, bound the type I protein phosphatase (PP1) and the adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase (PKA) holoenzyme. Anchored PP1 was active, limiting channel activity, whereas PKA activation overcame constitutive PP1 activity and conferred rapid enhancement of NMDA receptor currents. Hence, yotiao is a scaffold protein that physically attaches PP1 and PKA to NMDA receptors to regulate channel activity.

1 Howard Hughes Medical Institute, Vollum Institute, Oregon Health Sciences University, 3181 S.W. Sam Jackson Road, Portland, OR 97201, USA.
2 Howard Hughes Medical Institute and Department of Neurobiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
*   These authors contributed equally to this article.

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

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Recruitment of Protein Phosphatase 1 to the Nuclear Envelope by a-Kinase Anchoring Protein Akap149 Is a Prerequisite for Nuclear Lamina Assembly.
R. L. Steen, S. B. Martins, K. Tasken, and P. Collas (2000)
J. Cell Biol. 150, 1251-1262
   Abstract »    Full Text »    PDF »
The gamma -aminobutyric acid type A (GABAA) receptor-associated protein (GABARAP) promotes GABAA receptor clustering and modulates the channel kinetics.
L. Chen, H. Wang, S. Vicini, and R. W. Olsen (2000)
PNAS
   Abstract »    Full Text »
Spinophilin regulates the formation and function of dendritic spines.
J. Feng, Z. Yan, A. Ferreira, K. Tomizawa, J. A. Liauw, M. Zhuo, P. B. Allen, C. C. Ouimet, and P. Greengard (2000)
PNAS 97, 9287-9292
   Abstract »    Full Text »    PDF »
Sensitization Phenomena in Psychiatric Illness: Lessons from the Kindling Model.
J. E. Kraus (2000)
J Neuropsychiatry Clin Neurosci 12, 328-343
   Abstract »    Full Text »
Inhibition of the cAMP Pathway Decreases Early Long-Term Potentiation at CA1 Hippocampal Synapses.
N. A. Otmakhova, N. Otmakhov, L. H. Mortenson, and J. E. Lisman (2000)
J. Neurosci. 20, 4446-4451
   Abstract »    Full Text »    PDF »
Intracellular Modulation of NMDA Receptor Function by Antipsychotic Drugs.
J.-C. Leveque, W. Macias, A. Rajadhyaksha, R. R. Carlson, A. Barczak, S. Kang, X.-M. Li, J. T. Coyle, R. L. Huganir, S. Heckers, et al. (2000)
J. Neurosci. 20, 4011-4020
   Abstract »    Full Text »    PDF »
Developmentally Regulated NMDA Receptor-Dependent Dephosphorylation of cAMP Response Element-Binding Protein (CREB) in Hippocampal Neurons.
C. Sala, S. Rudolph-Correia, and M. Sheng (2000)
J. Neurosci. 20, 3529-3536
   Abstract »    Full Text »    PDF »
Protein Phosphatase-1 Regulation in the Induction of Long-Term Potentiation: Heterogeneous Molecular Mechanisms.
P. B. Allen, O. Hvalby, V. Jensen, M. L. Errington, M. Ramsay, F. A. Chaudhry, T. V. P. Bliss, J. Storm-Mathisen, R. G. M. Morris, P. Andersen, et al. (2000)
J. Neurosci. 20, 3537-3543
   Abstract »    Full Text »    PDF »
Protein-protein interactions define specificity in signal transduction.
T. Pawson and P. Nash (2000)
Genes & Dev. 14, 1027-1047
   Full Text »
Reversible Phosphorylation of the Signal Transduction Complex in Drosophila Photoreceptors.
M. Liu, L. L. Parker, B. E. Wadzinski, and B.-H. Shieh (2000)
J. Biol. Chem. 275, 12194-12199
   Abstract »    Full Text »    PDF »


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