Peptidyl prolyl cis-trans isomerase activity of cyclophilin A in functional homo-oligomeric receptor expression

Santosh Helekar, Jim Patrick

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

The functional expression of homo-oligomeric α7 neuronal nicotinic and type 3 serotonin receptors is dependent on the activity of a cyclophilin. In this paper we demonstrate that the mechanism of cyclophilin action during functional homo-oligomeric receptor expression in Xenopus oocytes is distinct from the calcineurin-dependent immunosuppressive mechanism by showing that a nonimmunosuppressive analog of cyclosporin A (CsA), SDZ 211-811, reduces functional receptor expression to the same extent as CsA. The cytoplasmic subtype of cyclophilin, cyclophilin A (CyPA), appears to be required for functional receptor expression. This is because overexpression of CyPA and a CyPA mutant that is deficient in CsA binding activity reverses CsA-induced reduction in functional receptor expression. The mechanism of action of CyPA is likely to involve its prolyl isomerase activity because a mutant CyPA with a single amino acid substitution (arginine 55 to alanine) that is predicted to produce a 1000-fold attenuation in isomerase activity fails to reverse the cyclosporin A effect. Our data also suggest that CyPA does not form a stable complex with receptor subunits.

Original languageEnglish (US)
Pages (from-to)5432-5437
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number10
DOIs
StatePublished - May 13 1997

Keywords

  • α7 nicotinic receptor
  • 5HT receptor
  • cyclosporin A
  • molecular chaperone
  • protein folding

ASJC Scopus subject areas

  • Genetics
  • General

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