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.
Brenman
J E
JE
Department of Physiology, School of Medicine, University of California at San Fancisco, California 94143, USA.
Chao
D S
DS
Gee
S H
SH
McGee
A W
AW
Craven
S E
SE
Santillano
D R
DR
Wu
Z
Z
Huang
F
F
Xia
H
H
Peters
M F
MF
Froehner
S C
SC
Bredt
D S
DS
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
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