Phosphorylation of the Nicotinic Acetylcholine Receptor and Localization of Its Phosphorylation Sites

Abstract

The nicotinic acetylcholine receptor (AChR) mediates synaptic transmission at the post-synaptic membrane of nicotinic cholinergic synapses. This receptor is a prototype of the chemically-gated ion channel receptors which contain the ligand binding site as well as an intrinsic ion channel responsible for signal transduction (Hucho, 1986; Changeux et al., 1987). Phosphorylation of AChR has been implicated in playing a role in the regulation of its ion channeling. Cyclic AMP-elevating agents which activate the cAMP-dependent protein kinase (PKA), as well as phorbol esters, which activate the Ca2+/phospholipid-dependent protein kinase (PKC), were shown to enhance receptor desensitizaticn (Middleton et al., 1986; Albuquerque et al., 1986; Eusebi et al., 1985). It was postulated that direct phosphorylation of the AChR by these two kinases may result in the observed physiological response. Indeed, phosphorylation of the receptor was demonstrated in intact mammalian muscle cells and this phosphorylation was stimulated by cAMP and Ca2+ (Miles et al., 1987; Smith et al., 1987).