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PMID: 8922396 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Cloning and characterization of postsynaptic density 93, a nitric oxide synthase interacting protein.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 16 ·No. 23 ·1996-12-01 ·Pages 7407-15

Brenman JE, Christopherson KS, Craven SE, McGee AW, Bredt DS

Abstract

Nitric oxide (NO) formation in brain is regulated by the calcium/calmodulin dependence of neuronal NO synthase (nNOS). Calcium influx through NMDA-type glutamate receptors is efficiently coupled to nNOS activity, whereas many other intracellular calcium pathways are poorly coupled. To elucidate possible mechanisms responsible for this coupling, we performed yeast two-hybrid screening to identify proteins that interact with nNOS. Two nNOS interacting proteins were identified: the postsynaptic density proteins PSD-93 and PSD-95. Here, we report the cloning and characterization of PSD-93. PSD-93 is expressed in discrete neuronal populations as well as in specific non-neuronal cells, and it exhibits complex molecular diversity attributable to tissue-specific alternative splicing. PSD-93, like PSD-95, binds to nNOS and to the NMDA receptor 2B. PSD-93, however, is unique among PSD-95/SAP-90 family members in its expression in Purkinje neuron cell bodies and dendrites. We also demonstrate that the PDZ domain at the N terminus of nNOS is required, but it is not sufficient for interaction with PSD-93/95. Given that PSD-93 and PSD-95 each contain multiple potential binding sites for nNOS and the NMDA receptor, complexes involving oligomers of PSD-93/95 may help account for the functional as well as the physical coupling of nNOS to NMDA receptors.

MeSH Terms
Alternative Splicing Amino Acid Sequence Animals Base Sequence Cerebellum/metabolism,ultrastructure Cloning, Molecular Dendrites/metabolism Disks Large Homolog 4 Protein Humans Intracellular Signaling Peptides and Proteins Membrane Proteins Molecular Sequence Data Nerve Tissue Proteins/genetics,metabolism Neurons/metabolism Nitric Oxide Synthase/metabolism Purkinje Cells/metabolism RNA, Messenger/metabolism Rats Rats, Sprague-Dawley
Chemicals
Disks Large Homolog 4 Protein Dlg4 protein, rat Intracellular Signaling Peptides and Proteins Membrane Proteins Mpp2 protein, rat Nerve Tissue Proteins RNA, Messenger postsynaptic density proteins Nitric Oxide Synthase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Brenman J E
Department of Physiology, University of California at San Francisco School of Medicine, 94143-0444, USA.
Christopherson K S
Craven S E
McGee A W
Bredt D S
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1996-12-01
Pages
7407-15
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6579097
Subset
IM
Databases
GENBANK
U50717
External Links
PubMed source PMC Full Text View journal details
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