Regulation of the Nicotinic Acetylcholine Receptor by Protein Phosphorylation

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Abstract
The nicotinic acetylcholine receptor is a multisubunit (α2βγδ) neurotransmitter-dependent ion channel that mediates synaptic transmission at the postsynaptic membrane of nicotinic cholinergic synapses. The nicotinic acetylcholine receptor is multiply phosphorylated by at least three different protein kinases (cAMP-dependent protein kinase protein kinase C, and a tyrosine-specific protein kinase) in postsynaptic membranes isolated from Torpedo californica. The cAMP-dependent protein kinase phosphorylates the γ and δ subunits of the receptor, while protein kinase C phosphorylates the δ and α subunits and the tyrosine-specific protein kinase phosphorylates the β, γ and δ subunits. In addition, the nicotinic acetylcholine receptor in rat myotubes is phosphorylated in intact primary muscle cell cultures and the phosphorylation of the receptor is regulated by forskolin, a potent activator of adenylate cyclase. Forskolin stimulates the phosphorylation of the α, γ and δ subunits of rat nicotinic receptor. The functional significance of phosphorylation of the nicotinic acetylcholine receptor has recently been examined by analyzing the properties of the purified and reconstituted Torpedo receptor after phosphorylation of the receptor. Phosphorylation of the γ and δ subunits of the receptor by cAMP-dependent protein kinase dramatically increased the rate of desensitization of the receptor, the process by which the receptor is inactivated in the presence of acetylcholine.

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