Acetylcholine receptor assembly is stimulated by phosphorylation of its γ subunit

• Published in: Neuron (Cambridge, Mass.) Vol. 7; no. 4; pp. 659 - 666
• Main Authors: Green, William N., Ross, Anthony F., Claudio, Toni
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 01.10.1991; Cell Press
• Subjects: Animals; Biological and medical sciences; Cell receptors; Cell structures and functions; Colforsin - pharmacology; Fundamental and applied biological sciences. Psychology; Molecular and cellular biology; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine); Phosphorylation; Receptors, Cholinergic - chemistry; Receptors, Cholinergic - metabolism; Receptors, Cholinergic - physiology; Time Factors; Up-Regulation; Phosphorylation; Cholinergic receptor; Gamma-Peptide chain; Cell line; Molecular assembly; Nicotinic receptor
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/0896-6273(91)90378-D

Different combinations of Torpedo acetylcholine receptor (AChR) subunits stably expressed in mouse fibroblasts were used to establish a role for phosphorylation in AChR biogenesis. When cell lines expressing fully functional AChR complexes ( α 2 βγδ) were labeled with 32P, only γ and δ subunits were phosphoryaated. Forskolin, which causes a 2- to 3-fold increase in AChR expression by stimulating subunit assembly, increased unassembled γ phosphorylation, but had little effect on unassembled δ. The forskolin effect on subunit phosphorylation was rapid, significantly preceding its effect on expression. The pivotal role of the γ subunit was established by treating αβγ and αβδ cell lines with forskolin and observing increased expression of only αβγ complexes. This effect was also observed in αγ, but not αδ cells. We conclude that the cAMP-induced increase in expression of cell surface AChRs is due to phosphorylation of unassembled γ subunits, which leads to increased efficiency of assembly of all four subunits.