title: Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domains.
abstract: 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.
authors.affiliation: Department of Physiology, School of Medicine, University of California at San Fancisco, California 94143, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Brenman
authors.forename: D S
authors.initials: DS
authors.lastname: Chao
authors.forename: S H
authors.initials: SH
authors.lastname: Gee
authors.forename: A W
authors.initials: AW
authors.lastname: McGee
authors.forename: S E
authors.initials: SE
authors.lastname: Craven
authors.forename: D R
authors.initials: DR
authors.lastname: Santillano
authors.forename: Z
authors.initials: Z
authors.lastname: Wu
authors.forename: F
authors.initials: F
authors.lastname: Huang
authors.forename: H
authors.initials: H
authors.lastname: Xia
authors.forename: M F
authors.initials: MF
authors.lastname: Peters
authors.forename: S C
authors.initials: SC
authors.lastname: Froehner
authors.forename: D S
authors.initials: DS
authors.lastname: Bredt
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002462:Cell Membrane / Q000378:metabolism; D017931:DNA Primers; D000076122:Disks Large Homolog 4 Protein; D004622:Embryo, Mammalian; D005091:Exons; D015870:Gene Expression; D051528:Guanylate Kinases; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008961:Models, Structural; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins
chemical_list: D002135:Calcium-Binding Proteins; D017931:DNA Primers; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C501451:Mpp2 protein, rat; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; C033652:postsynaptic density proteins; C091825:syntrophin alpha1; D019001:Nitric Oxide Synthase; C496468:DLG2 protein, human; D051528:Guanylate Kinases