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      CAPON: a protein associated with neuronal nitric oxide synthase that regulates its interactions with PSD95.

      Neuron
      Adaptor Proteins, Signal Transducing, Animals, Binding, Competitive, Brain, metabolism, Carrier Proteins, genetics, physiology, Cloning, Molecular, Drug Interactions, Guanylate Kinase, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, enzymology, Nitric Oxide Synthase, Rats, Rats, Sprague-Dawley, Tissue Distribution

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          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.

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