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

Neuron. 1994 Jan;12(1):179-89. doi: 10.1016/0896-6273(94)90162-7.

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 alpha 7 without blocking alpha 7 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 alpha 7 receptor could be rescued from cyclosporin A blockade by coexpressed muscle non-alpha 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Isomerases / biosynthesis
  • Amino Acid Isomerases / metabolism*
  • Animals
  • Blotting, Western
  • Brain / metabolism*
  • Bungarotoxins / metabolism
  • Calcimycin / pharmacology
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / metabolism*
  • Cloning, Molecular
  • Cyclosporine / pharmacology
  • DNA, Complementary / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Gene Expression
  • Ion Channels / biosynthesis*
  • Ion Channels / drug effects
  • Ion Channels / isolation & purification
  • Luciferases / biosynthesis
  • Luciferases / metabolism
  • Membrane Potentials / drug effects
  • Muscles / metabolism
  • Oocytes / drug effects
  • Oocytes / physiology
  • Peptidylprolyl Isomerase
  • Rats
  • Receptors, Serotonin / biosynthesis*
  • Receptors, Serotonin / drug effects
  • Tacrolimus / pharmacology
  • Xenopus laevis

Substances

  • Bungarotoxins
  • Carrier Proteins
  • DNA, Complementary
  • Ion Channels
  • Receptors, Serotonin
  • Calcimycin
  • Cyclosporine
  • Luciferases
  • Amino Acid Isomerases
  • Peptidylprolyl Isomerase
  • Tacrolimus