 |
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, February 1, 1999, 19(3):974-986
Protein Kinase C Modulation of Recombinant NMDA Receptor Currents: Roles for the C-Terminal C1 Exon and Calcium Ions
Stephen M. Logan1, Felix E. Rivera2, and John P. Leonard1 1 Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois 60607-7056, and 2 Department of Biology, Cayey University College, Cayey, Puerto Rico 00736
Protein kinase C (PKC) positively modulates NMDA receptor (NMDAR) currents. In contrast to previous reports, this study determines the importance of individual exons in the mechanism underlying the potentiation process by examining the complete set of eight naturally occurring splice variants expressed in Xenopus oocytes both as homomers and as heteromeric NR1/NR2A or NR1/NR2B complexes. After PKC stimulation, homomeric currents demonstrated a high level of potentiation (~500% of untreated baseline currents) that reduced to a lower level (~300% of baseline) in variants containing the first C-terminal exon (C1). An ANOVA showed that only C1 and no other exon or interaction of exons determined the degree of NMDAR current modulation by PKC. When recordings were performed in solutions in which barium replaces calcium, only the lower form of potentiation was observed, regardless of the splice variant exon composition. This suggested an important role for calcium in the PKC modulation of homomeric NMDA splice variant currents in which the C1 exon also participates. The effectiveness of the C1 exon to reduce the higher form of potentiation is modulated by heteromeric assemblies with NR2A heteromers yielding smaller levels of potentiation and a larger C1 exon effect compared with NR2B heteromers. The heteromers demonstrated the higher form of potentiation even in the absence of calcium. Furthermore, calcium had different effects in the potentiation of the heteromers depending on the NR2 subunit. This study refines the region of the NR1 subunit involved in a modulation crucial to the function of NMDA receptors and provides evidence that the NR2A and NR2B subunits realize this modulation differentially.
Key words: NR1; NR2; NMDAR; alternative splicing; variants; Xenopus oocytes; barium; phorbol ester; homomer; heteromer
Copyright © 1999 Society for Neuroscience 0270-6474/99/193974-13$05.00/0
This article has been cited by other articles:
S. Moriguchi, N. Shioda, H. Maejima, X. Zhao, W. Marszalec, J. Z. Yeh, K. Fukunaga, and T. Narahashi
Nefiracetam Potentiates N-Methyl-D-aspartate (NMDA) Receptor Function via Protein Kinase C Activation and Reduces Magnesium Block of NMDA Receptor
Mol. Pharmacol., February 1, 2007; 71(2): 580 - 587.
[Abstract] [Full Text] [PDF]
S. Moriguchi, X. Zhao, W. Marszalec, J. Z. Yeh, and T. Narahashi
Modulation of N-Methyl-D-aspartate Receptors by Donepezil in Rat Cortical Neurons
J. Pharmacol. Exp. Ther., October 1, 2005; 315(1): 125 - 135.
[Abstract] [Full Text] [PDF]
S. Moriguchi, W. Marszalec, X. Zhao, J. Z. Yeh, and T. Narahashi
Mechanism of Action of Galantamine on N-Methyl-D-Aspartate Receptors in Rat Cortical Neurons
J. Pharmacol. Exp. Ther., September 1, 2004; 310(3): 933 - 942.
[Abstract] [Full Text] [PDF]
B. R. Jarabek, R. P. Yasuda, and B. B. Wolfe
Regulation of proteins affecting NMDA receptor-induced excitotoxicity in a Huntington's mouse model
Brain, March 1, 2004; 127(3): 505 - 516.
[Abstract] [Full Text] [PDF]
S. M. Clinton, V. Haroutunian, K. L. Davis, and J. H. Meador-Woodruff
Altered Transcript Expression of NMDA Receptor-Associated Postsynaptic Proteins in the Thalamus of Subjects With Schizophrenia
Am J Psychiatry, June 1, 2003; 160(6): 1100 - 1109.
[Abstract] [Full Text] [PDF]
G. K. Seabold, A. Burette, I. A. Lim, R. J. Weinberg, and J. W. Hell
Interaction of the Tyrosine Kinase Pyk2 with the N-Methyl-D-aspartate Receptor Complex via the Src Homology 3 Domains of PSD-95 and SAP102
J. Biol. Chem., April 18, 2003; 278(17): 15040 - 15048.
[Abstract] [Full Text] [PDF]
G.-Y. Liao, D. A. Wagner, M. H. Hsu, and J. P. Leonard
Evidence for Direct Protein Kinase-C Mediated Modulation of N-Methyl-D-aspartate Receptor Current
Mol. Pharmacol., April 16, 2001; 59(5): 960 - 964.
[Abstract] [Full Text]
M. B. Gingrich, C. E. Junge, P. Lyuboslavsky, and S. F. Traynelis
Potentiation of NMDA Receptor Function by the Serine Protease Thrombin
J. Neurosci., June 15, 2000; 20(12): 4582 - 4595.
[Abstract] [Full Text] [PDF]
F. Taverna, Z.-g. Xiong, L. Brandes, J. C. Roder, M. W. Salter, and J. F. MacDonald
The Lurcher Mutation of an alpha -Amino-3-hydroxy-5-methyl- 4-isoxazolepropionic Acid Receptor Subunit Enhances Potency of Glutamate and Converts an Antagonist to an Agonist
J. Biol. Chem., March 17, 2000; 275(12): 8475 - 8479.
[Abstract] [Full Text] [PDF]
X. Zheng, L. Zhang, A. P. Wang, M. V. L. Bennett, and R. S. Zukin
Protein kinase C potentiation of N-methyl-D-aspartate receptor activity is not mediated by phosphorylation of N-methyl-D-aspartate receptor subunits
PNAS, December 21, 1999; 96(26): 15262 - 15267.
[Abstract] [Full Text] [PDF]
M. Kumari
Differential Effects of Chronic Ethanol Treatment on N-Methyl-D-aspartate R1 Splice Variants in Fetal Cortical Neurons
J. Biol. Chem., August 3, 2001; 276(32): 29764 - 29771.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|