CAPON: a protein associated with neuronal nitric oxide synthase

摘要

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 influences nNOS by regulating its ability to associate with PSD95/NMDA receptor complexes.