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Activation of m 1 Muscarinic Acetylcholine Receptor Regulates τ Phosphorylation in Transfected PC12 Cells
Author(s) -
Sadot Einat,
Gurwitz David,
Barg Jacob,
Behar Leah,
Ginzburg Irith,
Fisher Abraham
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.66020877.x
Subject(s) - muscarinic acetylcholine receptor , phosphorylation , muscarinic acetylcholine receptor m4 , muscarinic acetylcholine receptor m3 , muscarinic acetylcholine receptor m5 , muscarinic acetylcholine receptor m1 , microbiology and biotechnology , acetylcholine , muscarinic acetylcholine receptor m2 , acetylcholine receptor , chemistry , carbachol , cholinergic , biology , transfection , medicine , receptor , endocrinology , biochemistry , gene
Hyperphosphorylated τ proteins are the principal fibrous component of the neurofibrillary tangle pathology in Alzheimer's disease. The possibility that τ phosphorylation is controlled by cell surface neurotransmitter receptors was examined in PC12 cells transfected with the gene for the rat m 1 muscarinic acetylcholine receptor. Stimulation of m 1 receptor in these cells with two acetylcholine agonists, carbachol and AF102B, decreased τ phosphorylation, as indicated by specific τ monoclonal antibodies that recognize phosphorylation‐dependent epitopes and by alkaline phosphatase treatment. The muscarinic effect was both time and dose dependent. In addition, a synergistic effect on τ phosphorylation was found between treatments with muscarinic agonists and nerve growth factor. These studies provide the first evidence for a link between the cholinergic signal transduction system and the neuronal cytoskeleton that can be mediated by regulated phosphorylation of τ microtubule‐associated protein.