Interaction of neuronal nitric-oxide synthase with caveolin-3 in skeletal muscle

Identification of a novel caveolin scaffolding/inhibitory domain

Virginia J. Venema, Hong Ju, Rong Zou, Richard C Venema

Research output: Contribution to journalArticle

207 Citations (Scopus)

Abstract

Neuronal nitric-oxide synthase (nNOS) has been shown previously to interact with α1-syntrophin in the dystrophin complex of skeletal muscle. In the present study, we have examined whether nNOS also interacts with caveolin-3 in skeletal muscle. nNOS and caveolin-3 are coimmunoprecipitated from rat skeletal muscle homogenates by antibodies directed against either of the two proteins. Synthetic peptides corresponding to the membrane-proximal caveolin-3 residues 65-84 and 109-130 and homologous caveolin-1 residues 82- 101 and 135-156 potently inhibit the catalytic activity of purified, recombinant nNOS. Purified nNOS also binds to a glutathione S-transferase- caveolin-1 fusion protein in in vitro binding assays. In vitro binding is completely abolished by preincubation of nNOS with either of the two caveolin-3 inhibitory peptides. Interactions between nNOS and caveolin-3, therefore, appear to be direct and to involve two distinct caveolin scaffolding/inhibitory domains. Other caveolin-interacting enzymes, including endothelial nitric-oxide synthase and the c-Src tyrosine kinase, are also potently inhibited by each of the four caveolin peptides. Inhibitory interactions mediated by two different caveolin domains may thus be a general feature of enzyme docking to caveolin proteins in plasmalemmal caveolae.

Original languageEnglish (US)
Pages (from-to)28187-28190
Number of pages4
JournalJournal of Biological Chemistry
Volume272
Issue number45
DOIs
StatePublished - Nov 7 1997

Fingerprint

Caveolin 3
Caveolins
Nitric Oxide Synthase Type I
Muscle
Skeletal Muscle
Caveolin 1
Peptides
Caveolae
Dystrophin
Nitric Oxide Synthase Type III
Enzymes
Glutathione Transferase
Rats
Assays
Catalyst activity
Proteins
Fusion reactions
Membranes
Antibodies

ASJC Scopus subject areas

  • Biochemistry

Cite this

Interaction of neuronal nitric-oxide synthase with caveolin-3 in skeletal muscle : Identification of a novel caveolin scaffolding/inhibitory domain. / Venema, Virginia J.; Ju, Hong; Zou, Rong; Venema, Richard C.

In: Journal of Biological Chemistry, Vol. 272, No. 45, 07.11.1997, p. 28187-28190.

Research output: Contribution to journalArticle

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