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 α-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/α-subunit complex in stably transfected fibroblasts revealed that Bip associates with newly synthesized unassembled α-subunit and some αγ and αδ subunit complexes. Significantly, Bip does not associate well with the more mature form of the α-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.