Interaction of Nitric Oxide Synthase With the Postsynaptic Density Protein PSD-95 and alpha1-syntrophin Mediated by PDZ Domains

Cell. 1996 Mar 8;84(5):757-67. doi: 10.1016/s0092-8674(00)81053-3.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Brain / embryology
  • Brain / metabolism*
  • Calcium-Binding Proteins
  • Cell Membrane / metabolism
  • DNA Primers
  • Disks Large Homolog 4 Protein
  • Embryo, Mammalian
  • Exons
  • Gene Expression
  • Guanylate Kinases
  • In Situ Hybridization
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Models, Structural
  • Molecular Sequence Data
  • Muscle Proteins / chemistry
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / metabolism
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism*
  • Nitric Oxide Synthase / biosynthesis
  • Nitric Oxide Synthase / chemistry
  • Nitric Oxide Synthase / metabolism*
  • Organ Specificity
  • Polymerase Chain Reaction
  • Protein Conformation
  • RNA, Messenger / biosynthesis
  • Rats
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • Tumor Suppressor Proteins

Substances

  • Calcium-Binding Proteins
  • DNA Primers
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Mpp2 protein, rat
  • Muscle Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Tumor Suppressor Proteins
  • postsynaptic density proteins
  • syntrophin alpha1
  • Nitric Oxide Synthase
  • DLG2 protein, human
  • Guanylate Kinases

Associated data

  • GENBANK/U50717