Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domains.
Neuronal nitric oxide synthase (nNOS) is concentrated at synaptic junctions in brain and motor endplates in skeletal muscle. Here, we show that the N-terminus of nNOS, which contains a PDZ protein motif, interacts with similar motifs in postsynaptic density-95 protein (PSD-95) and a related novel protein, PSD-93.nNOS and PSD-95 are coexpressed in numerous neuronal populations, and a PSD-95/nNOS complex occurs in cerebellum. PDZ domain interactions also mediate binding of nNOS to skeletal muscle syntrophin, a dystrophin-associated protein. nNOS isoforms lacking a PDZ domain, identified in nNOSdelta/delta mutant mice, do not associate with PSD-95 in brain or with skeletal muscle sarcolemma. Interaction of PDZ-containing domains therefore mediates synaptic association of nNOS and may play a more general role in formation of macromolecular signaling complexes.
Pubmed ID: 8625413 RIS Download
Amino Acid Sequence | Animals | Base Sequence | Binding Sites | Brain | Calcium-Binding Proteins | Cell Membrane | DNA Primers | Embryo, Mammalian | Exons | Gene Expression | Guanylate Kinase | In Situ Hybridization | Intracellular Signaling Peptides and Proteins | Membrane Proteins | Models, Structural | Molecular Sequence Data | Muscle Proteins | Muscle, Skeletal | Nerve Tissue Proteins | Neurons | Nitric Oxide Synthase | Organ Specificity | Polymerase Chain Reaction | Protein Conformation | RNA, Messenger | Rats | Recombinant Fusion Proteins | Signal Transduction | Tumor Suppressor Proteins