Membrane Tethering Enables an Extracellular Domain of the Acetylcholine Receptor α Subunit to Form a Heterodimeric Ligand-Binding Site

• Published in: The Journal of cell biology 1996-11, Vol.135 (3), p.809-817
• Main Authors: Wang, Zuo-Zhong, Hardy, Stephen F., Hall, Zach W.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antibodies; Binding Sites; Brefeldin A; Bungarotoxins - metabolism; Cells; Cellular biology; Cholinergic receptors; Complementary DNA; COS Cells; Cyclopentanes - pharmacology; Dimerization; Endoplasmic Reticulum - chemistry; Glycosylphosphatidylinositols - analysis; Intracellular Membranes - metabolism; Ligands; Membrane proteins; Membranes; Mice; Molecular Sequence Data; Neurons; Nicotinic receptors; P branes; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Protein Conformation; Protein Folding; Protein Synthesis Inhibitors - pharmacology; Proteins; Receptors, Nicotinic - chemistry; Receptors, Nicotinic - metabolism; T lymphocytes
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.135.3.809

The first step of assembly of the nicotinic acetylcholine receptor (AChR) of adult skeletal muscle is the specific association of the α subunit with either δ or ε subunits to form a heterodimer with a ligand-binding site. Previous experiments have suggested that heterodimer formation in the ER arises from interaction between the luminal, NH2-terminal domains of the subunits. When expressed in COS cells with the δ subunit, however, the truncated NH2-terminal domain of the α subunit folded correctly but did not form a heterodimer. Association with the δ subunit occurred only when the NH2-terminal domain was retained in the ER and was tethered to the membrane by its own M1 transmembrane domain, by the transmembrane domain of another protein, or by a glycolipid link. In each case, the ligand-binding sites of the resulting heterodimers were indistinguishable from that formed when the full-length α subunit was used. Attachment to the membrane may promote interaction by concentrating or orienting the subunit; alternatively, a membrane-bound factor may facilitate subunit association.