Abstract
Nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) is important for N-methyl-D-aspartate (NMDA) receptor-dependent neurotransmitter release, neurotoxicity, and cyclic GMP elevations. The coupling of NMDA receptor-mediated calcium influx and nNOS activation is postulated to be due to a physical coupling of the receptor and the enzyme by an intermediary adaptor protein, PSD95, through a unique PDZ-PDZ domain interaction between PSD95 and nNOS. Here, we report the identification of a novel nNOS-associated protein, CAPON, which is highly enriched in brain and has numerous colocalizations with nNOS. CAPON interacts with the nNOS PDZ domain through its C terminus. CAPON competes with PSD95 for interaction with nNOS, and overexpression of CAPON results in a loss of PSD95/nNOS complexes in transfected cells. CAPON may influence nNOS by regulating its ability to associate with PSD95/NMDA receptor complexes.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Animals
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Binding, Competitive
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Brain / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Carrier Proteins / physiology*
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Cloning, Molecular
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Disks Large Homolog 4 Protein
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Drug Interactions
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Guanylate Kinases
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Molecular Sequence Data
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Nerve Tissue Proteins / metabolism
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Nerve Tissue Proteins / physiology*
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Neurons / enzymology*
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Nitric Oxide Synthase / genetics
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Nitric Oxide Synthase / metabolism*
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Rats
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Rats, Sprague-Dawley
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Tissue Distribution
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Disks Large Homolog 4 Protein
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Dlg4 protein, mouse
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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NOS1AP protein, rat
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Nerve Tissue Proteins
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Nos1ap protein, mouse
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postsynaptic density proteins
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Nitric Oxide Synthase
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Guanylate Kinases
Associated data
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GENBANK/AF037070
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GENBANK/AF037071