Activation of m1 muscarinic acetylcholine receptor regulates τ phosphorylation in transfected PC12 cells

Einat Sadot, David Gurwitz, Jacob Barg, Leah Behar, Irith Ginzburg, Abraham Fisher

Research output: Contribution to journalArticlepeer-review

Abstract

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 m1 muscarinic acetylcholine receptor. Stimulation of m1 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.

Original languageEnglish
Pages (from-to)877-880
Number of pages4
JournalJournal of Neurochemistry
Volume66
Issue number2
DOIs
StatePublished - Feb 1996

Keywords

  • AF102B
  • Alzheimer's disease
  • Carbachol
  • Nerve growth factor
  • m muscarinic receptor
  • τ protein

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