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 language | English (US) |
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Pages (from-to) | 179-189 |
Number of pages | 11 |
Journal | Neuron |
Volume | 12 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1994 |
ASJC Scopus subject areas
- Neuroscience(all)