CAPON - A PROTEIN ASSOCIATED WITH NEURONAL NITRIC-OXIDE SYNTHASE THATREGULATES ITS INTERACTIONS WITH PSD95

Nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) is important for N-methyl-D-aspartate (NMDA) receptor-dependent neurotra nsmitter release, neurotoxicity, and cyclic GMP elevations. The coupli ng of NMDA receptor-mediated calcium influx and nNOS activation is pos tulated to be due to a physical coupling of the receptor and the enzym e by an intermediary adaptor protein, PSD95, through a unique PDZ-PDZ domain interaction between PSD95 and nNOS. Here, we report the identif ication of a novel nNOS-associated protein, CAPON, which is highly enr iched in brain and has numerous colocalizations with nNOS. CAPON inter acts with the nNOS PDZ domain through its C terminus. CAPON competes w ith PSD95 for interaction with nNOS, and overexpression of CAPON resul ts in a loss of PSD95/nNOS complexes in transfected cells. CAPON may i nfluence nNOS by regulating its ability to associate with PSD95/NMDA r eceptor complexes.