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J Biol Chem, Vol. 274, Issue 39, 27467-27473, September 24, 1999
,
From the Departments of Nitric oxide (NO) biosynthesis in cerebellum is
preferentially activated by calcium influx through
N-methyl-D-aspartate (NMDA)-type glutamate
receptors, suggesting that there is a specific link between these
receptors and neuronal NO synthase (nNOS). Here, we find that PSD-95
assembles a postsynaptic protein complex containing nNOS and NMDA
receptors. Formation of this complex is mediated by the PDZ domains of
PSD-95, which bind to the COOH termini of specific NMDA receptor
subunits. In contrast, nNOS is recruited to this complex by a novel
PDZ-PDZ interaction in which PSD-95 recognizes an internal motif
adjacent to the consensus nNOS PDZ domain. This internal motif is a
structured "pseudo-peptide" extension of the nNOS PDZ that
interacts with the peptide-binding pocket of PSD-95 PDZ2. This
asymmetric interaction leaves the peptide-binding pocket of the nNOS
PDZ domain available to interact with additional COOH-terminal PDZ
ligands. Accordingly, we find that the nNOS PDZ domain can bind PSD-95
PDZ2 and a COOH-terminal peptide simultaneously. This bivalent nature
of the nNOS PDZ domain further expands the scope for assembly of
protein networks by PDZ domains.
Physiology and
§ Cellular and Molecular Pharmacology, and Program in
Biomedical Sciences, University of California,
San Francisco, California 94143-0444
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F. Imamura, S. Maeda, T. Doi, and Y. Fujiyoshi Ligand Binding of the Second PDZ Domain Regulates Clustering of PSD-95 with the Kv1.4 Potassium Channel J. Biol. Chem., January 25, 2002; 277(5): 3640 - 3646. [Abstract] [Full Text] [PDF]
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Q. Zhang, J.-S. Fan, and M. Zhang Interdomain Chaperoning between PSD-95, Dlg, and Zo-1 (PDZ) Domains of Glutamate Receptor-interacting Proteins J. Biol. Chem., November 9, 2001; 276(46): 43216 - 43220. [Abstract] [Full Text] [PDF]
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C. Rampon, C. H. Jiang, H. Dong, Y.-P. Tang, D. J. Lockhart, P. G. Schultz, J. Z. Tsien, and Y. Hu Effects of environmental enrichment on gene expression in the brain PNAS, November 7, 2000; 97(23): 12880 - 12884. [Abstract] [Full Text] [PDF]
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S. Ghatan, S. Larner, Y. Kinoshita, M. Hetman, L. Patel, Z. Xia, R. J. Youle, and R. S. Morrison p38 MAP Kinase Mediates Bax Translocation in Nitric Oxide-induced Apoptosis in Neurons J. Cell Biol., July 24, 2000; 150(2): 335 - 348. [Abstract] [Full Text] [PDF]
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M. Gotthardt, M. Trommsdorff, M. F. Nevitt, J. Shelton, J. A. Richardson, W. Stockinger, J. Nimpf, and J. Herz Interactions of the Low Density Lipoprotein Receptor Gene Family with Cytosolic Adaptor and Scaffold Proteins Suggest Diverse Biological Functions in Cellular Communication and Signal Transduction J. Biol. Chem., August 11, 2000; 275(33): 25616 - 25624. [Abstract] [Full Text] [PDF]
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M. Russwurm, N. Wittau, and D. Koesling Guanylyl Cyclase/PSD-95 Interaction. TARGETING OF THE NITRIC OXIDE-SENSITIVE alpha 2beta 1 GUANYLYL CYCLASE TO SYNAPTIC MEMBRANES J. Biol. Chem., November 21, 2001; 276(48): 44647 - 44652. [Abstract] [Full Text] [PDF]
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L. A. Hu, W. Chen, R. T. Premont, M. Cong, and R. J. Lefkowitz G Protein-coupled Receptor Kinase 5 Regulates beta 1-Adrenergic Receptor Association with PSD-95 J. Biol. Chem., January 4, 2002; 277(2): 1607 - 1613. [Abstract] [Full Text] [PDF]
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S. R. Jaffrey, F. Benfenati, A. M. Snowman, A. J. Czernik, and S. H. Snyder Neuronal nitric-oxide synthase localization mediated by a ternary complex with synapsin and CAPON PNAS, March 5, 2002; 99(5): 3199 - 3204. [Abstract] [Full Text] [PDF]
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 D. Saur, W. L. Neuhuber, B. Gengenbach, A. Huber, V. Schusdziarra, and H.-D. Allescher Site-specific gene expression of nNOS variants in distinct functional regions of rat gastrointestinal tract Am J Physiol Gastrointest Liver Physiol, February 1, 2002; 282(2): G349 - G358. [Abstract] [Full Text] [PDF]
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