N-linked glycosylation is required for nicotinic receptor assembly but not for subunit associations with calnexin

J Biol Chem. 2005 Oct 7;280(40):33800-10. doi: 10.1074/jbc.M501813200. Epub 2005 Aug 9.

Abstract

We investigated how asparagine (N)-linked glycosylation affects assembly of acetylcholine receptors (AChRs) in the endoplasmic reticulum (ER). Block of N-linked glycosylation inhibited AChR assembly whereas block of glucose trimming partially blocked assembly at the late stages. Removal of each of seven glycans had a distinct effect on AChR assembly, ranging from no effect to total loss of assembly. Because the chaperone calnexin (CN) associates with N-linked glycans, we examined CN interactions with AChR subunits. CN rapidly associates with 50% or more of newly synthesized AChR subunits, but not with subunits after maturation. Block of N-linked glycosylation or trimming did not alter CN-AChR subunit associations nor did subunit mutations prevent N-linked glycosylation. Additionally, CN associations with subunits lacking N-linked glycans occurred without subunit aggregation or misfolding. Our data indicate that CN associates with AChR subunits without N-linked glycan interactions. Furthermore, CN-subunit associations only occur early in AChR assembly and have no role in events later that require N-linked glycosylation.

Publication types

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

MeSH terms

  • Asparagine / metabolism
  • Calnexin / physiology*
  • Cell Line
  • Endoplasmic Reticulum / physiology*
  • Glucose / metabolism
  • Glycosylation
  • Humans
  • Kidney / cytology
  • Polysaccharides / metabolism
  • Protein Conformation
  • Protein Folding
  • Protein Processing, Post-Translational
  • Receptors, Nicotinic / biosynthesis*
  • Receptors, Nicotinic / chemistry*

Substances

  • Polysaccharides
  • Receptors, Nicotinic
  • Calnexin
  • Asparagine
  • Glucose