BIP associates with newly synthesized subunits of the mouse muscle nicotinic receptor.
A slow conformational change in newly synthesized acetylcholine receptor subunits is thought to be a requisite step in the biogenesis of this multi-subunit transmembrane glycoprotein. Previously, we demonstrated that this early conformational change within the alpha-subunit was inefficient and dependent upon disulfide bond formation (Blount, P. and J.P. Merlie. 1990. J. Cell Biol. 111:2613-2622). Here we show that newly synthesized acetylcholine receptor subunits and subunit complexes in the muscle-like cell line, BC3H-1, are associated with Bip, a ubiquitous binding protein of the endoplasmic reticulum. Characterization of the Bip/alpha-subunit complex in stably transfected fibroblasts revealed that Bip associates with newly synthesized unassembled alpha-subunit and some alpha gamma and alpha delta subunit complexes. Significantly, Bip does not associate well with the more mature form of the alpha-subunit containing an intramolecular disulfide bridge. Hence, Bip may play an important role in the conformational maturation and/or editing of unassembled AChR subunits and subunit complexes in vivo.
Blount
P
P
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110.
Merlie
J P
JP
D000818:Animals; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D046911:Macromolecular Substances; D051379:Mice; D008809:Mice, Inbred C3H; D018832:Molecular Chaperones; D008970:Molecular Weight; D009132:Muscles / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D011978:Receptors, Nicotinic / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D014162:Transfection
D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D046911:Macromolecular Substances; D018832:Molecular Chaperones; D011978:Receptors, Nicotinic