Protein-tyrosine phosphatases specifically regulate muscle adult-type nicotinic acetylcholine receptor gene expression

• Published in: The Journal of biological chemistry 1994-11, Vol.269 (45), p.27811-27814
• Main Authors: Sapru, M K, Zhou, G, Goldman, D
• Format: Article
• Language: English
• Subjects: Aging; Animals; Calcimycin - pharmacology; Calcium - metabolism; Cells, Cultured; Chickens; Embryo, Nonmammalian; Gene Expression Regulation - drug effects; Motor Endplate - metabolism; Muscles - drug effects; Muscles - metabolism; Promoter Regions, Genetic; Protein Tyrosine Phosphatases - metabolism; Receptors, Nicotinic - biosynthesis; RNA, Messenger - analysis; RNA, Messenger - biosynthesis; Vanadates - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)46857-3

Innervation of skeletal muscles results in expression of adult-type nicotinic acetylcholine receptors (alpha 2 beta epsilon delta) beneath the neuromuscular junction. This local expression is largely a result of selective induction of adult-type nicotinic acetylcholine receptor (nAChR) genes in endplate-associated myonuclei. The molecular mechanism by which the nerve induces gene expression in these nuclei is not known. We have shown previously that ionophore-induced calcium influx across the plasma membrane preferentially decreases expression from the adult-type specific nAChR epsilon-subunit gene (Walke, W., Staple, J., Adams, L., Gnegy, M., Chahine, K., and Goldman, D. (1994) J. Biol. Chem. 269, 19447-19456). Here we provide evidence that the genes encoding adult-type nAChRs are specifically regulated by protein-tyrosine phosphatase activity. Orthovanadate, a specific protein-tyrosine phosphatase inhibitor, caused increased expression of the epsilon-subunit gene in rat primary myotubes and was able to completely block the suppressive effects of increased calcium influx on epsilon-subunit RNA expression. Overexpression of protein-tyrosine phosphatases selectively decreased expression from the adult-type nAChR genes with no effect on the embryonic-type specific gamma-subunit gene. These results demonstrate that protein-tyrosine phosphatases regulate mammalian adult-type nAChR gene expression and suggest a mechanism by which muscle innervation selectively regulates gene expression in endplate-associated myonuclei.