Prolyl isomerase requirement for the expression of functional homo-oligomeric ligand-gated ion channels

Santosh Helekar, David Char, Shawn Neff, Jim Patrick

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

Ligand-gated ion channel subunits show a striking abundance of highly conserved proline residues. We, therefore, tested the hypothesis that peptidyl-prolyl isomerases may be involved in the maturation of these channels. Cyclosporin A, a selective blocker of a ubiquitous isomerase cyclophilin, reduced the surface expression in Xenopus oocytes of functional homo-oligomeric receptors containing nicotinic acetylcholine receptor subunit α7 without blocking α7 polypeptide synthesis. This effect could be generalized to the homo-oligomeric 5-hydroxytryptamine type 3 receptor but not to the hetero-oligomeric muscle nicotinic receptor. An α7 receptor could be rescued from cyclosporin A blockade by coexpressed muscle non-α subunits. The effect of cyclosporin A was reversed by overexpression of exogenous rat brain cyclophilin. These findings indicate that cyclophilins may play a critical role in the maturation of homo-oligomeric receptors, acting directly or indirectly as prolyl isomerases or as molecular chaperones.

Original languageEnglish (US)
Pages (from-to)179-189
Number of pages11
JournalNeuron
Volume12
Issue number1
DOIs
StatePublished - Jan 1994

ASJC Scopus subject areas

  • Neuroscience(all)

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