Effects of inhibiting oligosaccharide trimming by 1-deoxynojirimycin on the nicotinic acetylcholine receptor
The nicotinic acetylcholine receptor has a subunit stoichiometry of ..cap alpha.. /sub 2/..beta gamma..delta; all 5 subunits contain N-linked oligosaccharides. The authors investigated what role trimming of the oligosaccharides played in the post-translational processing of the subunits and assembly of the receptor by examining the receptor synthesized in the presence of an inhibitor of oligosaccharide trimming, 1-deoxynojirimycin. BC3H-1 cells express one-third fewer receptors when grown in the presence of 1-deoxynojirimycin. The receptor subunits that are expressed have decreased mobility by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating an inhibition of oligosaccharide trimming. In control cells, 40% of the translated ..cap alpha.. subunit acquires the capacity to bind ..cap alpha..-bungarotoxin with a half-time of 40 min before assembly with the other subunits; the rest is rapidly degraded. In 1-deoxynojirimycin-treated cells approximately the same amount of ..cap alpha.. subunit is translated as in control cells, but that ..cap alpha.. subunit is degraded more rapidly, and only 25% acquires the capacity to bind ..cap alpha..-bungarotoxin. From these results, they conclude that oligosaccharide processing either may aid in protecting the ..cap alpha.. subunit primary translation product from degradation or may be required for the conformational change or other post-translational modifications(s) necessary for formation of the ..cap alpha..-bungarotoxin binding form of the ..cap alpha.. subunit, which is then protected from proteolytic degradation. The cell surface receptor that is expressed in the presence of 1-deoxynojirimycin, however, is not altered in its affinity for cholinergic ligands. Thus, they conclude that differential N-linked oligosaccharide trimming of the 2 ..cap alpha.. subunits does not appear to play a part in the differences in affinities of the 2 ..cap alpha.. subunits for cholinergic ligands.
- Research Organization:
- Washington Univ. School of Medicine, St. Louis, MO
- OSTI ID:
- 6934240
- Journal Information:
- J. Biol. Chem.; (United States), Vol. 261:31
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ENZYME INHIBITORS
BIOCHEMISTRY
OLIGOSACCHARIDES
RADIORECEPTOR ASSAY
RECEPTORS
MOLECULAR STRUCTURE
ACETYLCHOLINE
AFFINITY
ELECTROPHORESIS
INHIBITION
IODINE 125
METHIONINE
NICOTINIC ACID
SULFUR 35
AMINES
AMINO ACIDS
AMMONIUM COMPOUNDS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOHYDRATES
CARBOXYLIC ACIDS
CHEMISTRY
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ESTERS
EVEN-ODD NUCLEI
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LIPOTROPIC FACTORS
MEMBRANE PROTEINS
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PARASYMPATHOMIMETICS
PROTEINS
PYRIDINES
QUATERNARY COMPOUNDS
RADIOISOTOPES
SACCHARIDES
SULFUR ISOTOPES
TRACER TECHNIQUES
VITAMIN B GROUP
VITAMINS
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