Acetylcholine receptor-inducing factor from chicken brain increases the level of mRNA encoding the receptor alpha subunit.

Abstract

A 42-kDa glycoprotein isolated from chicken brain, referred to as acetylcholine receptor-inducing activity (ARIA), that stimulates the rate of incorporation of acetylcholine receptors into the surface of chicken myotubes may play a role in the nerve-induced accumulation of receptors at developing neuromuscular synapses. Using nuclease-protection assays, we have found that ARIA causes a 2- to 16-fold increase in the level of mRNA encoding the .alpha. subunit of the receptor, with little or no change in the levels of .gamma.- and .delta.-subunit messengers. ARIA also increases the amount of a putative nuclear precursor of .alpha.-subunit mRNA, consistent with an activation of gene transcription. These results suggest that the concentration of .alpha. subunit may limit the rate of biosynthesis of the acetylcholine receptors in chicken myotubes. They also indicate that neuronal factors can regulate the expression of receptor subunit genes in a selective manner. Tetrodotoxin, 8-bromo-cAMP, and forskolin also increase the amount of .alpha.-subunit mRNA, with little change in the amount of .gamma.- and .delta.-subunit mRNAs. Unlike ARIA, however, these agents have little effect on the concentration of the .alpha.-subunit nuclear precursor.