Molecular Biology of the Acetylcholine Receptor: Structure and Regulation of Biogenesis

Abstract

The recent remarkable progress in the molecular biology of the nicotinic acetycholine receptor (AChR) stems from a decade of intensive biochemical analysis. This in turn depended on the large quantities (ca. 100 mg/kg tissue) of pure receptor protein that can be obtained with relative ease from the electroplax organs of Torpedo sp. and, to a lesser extent, Electrophorus sp. The extensive characterization of this complex membrane protein has included the determination of its molecular weight, subunit composition, and stoichiometry; molecular dimensions and shape; arrangement of subunits and topology in the membrane; and identification of functional states [reviewed in Karlin, 1980; Conti-Troconi and Raftery, 1982; Changeux et al., 1984]. Of critical importance to molecular biology have been the determination of partial amino acid sequence [Raftery et al., 1980], preparation of subunit-specific antibodies [Claudio and Raftery, 1977; Lindstrom et al., 1978], affinity labeling [Karlin and Cowburn, 1973], and functional reconstitution [Nelson et al., 1980; Epstein and Racker, 1978]. The fact that no other channel-containing receptor has even approached this level of characterization illustrates how difficult and material-intensive such studies are. Indeed, although the vertebrate skeletal muscle AChR is comparatively well characterized [Nathanson and Hall, 1979; Sumikawa et al., 1982a], most of what is known about the molecular structure of the receptor at the neuromuscular junction is based on analogy to the electroplax AChR. For that reason, the majority of this discussion will be restricted to the Torpedo receptor.

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