A model for dynamic regulation of choline acetyltransferase by phosphorylation

• Published in: Journal of neurochemistry Vol. 95; no. 2; pp. 305 - 313
• Main Authors: Dobransky, Tomas, Rylett, R. Jane
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-10-2005; Blackwell
• Subjects: acetylcholine; Acetylcholine - biosynthesis; Amino Acid Sequence; Animals; binding motifs; Biological and medical sciences; choline acetyltransferase; Choline O-Acetyltransferase - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Fundamental and applied biological sciences. Psychology; Hormones and neuropeptides. Regulation; Humans; Hypothalamus. Hypophysis. Epiphysis. Urophysis; Medical sciences; Models, Biological; Molecular Sequence Data; Neurology; Phosphorylation; Protein Processing, Post-Translational; regulation; Vertebrates: endocrinology; Acyltransferases; Cholinergic neuron; Nervous system diseases; Phosphorylation; Enzyme; Alzheimer disease; Transferases; Central nervous system; Choline O-acetyltransferase; Cerebral disorder; Substrate; Signal transduction; choline acetyltransferase; regulation; binding motifs; Central nervous system disease; Neurotransmitter; Degenerative disease; Acetylcholine; Kinetics; Disruption; Mutation; Dynamic model; Neurological disorder
• DOI: 10.1111/j.1471-4159.2005.03367.x
• EISSN: 1471-4159
• ISSN: 0022-3042

Choline acetyltransferase (ChAT) synthesizes the neurotransmitter acetylcholine (ACh) and is a phenotypic marker for cholinergic neurons. Cholinergic neurons in brain are involved in cognitive function, attentional processing and motor control, and decreased ChAT activity is found in several neurological disorders including Alzheimer's disease. Dysregulation of ChAT and cholinergic communication is also associated with some spontaneous point‐mutations in ChAT that alter its substrate binding kinetics, or by disruption of signaling pathways that could regulate protein kinases for which ChAT is a substrate. It has been identified recently that the catalytic activity and subcellular distribution of ChAT, and its interaction with other cellular proteins, can be modified by phosphorylation of the enzyme by protein kinase‐C and Ca2+/calmodulin‐dependent protein kinase II; these kinases appear also to mediate some of the effects of β‐amyloid peptides on cholinergic neuron functions, including the effects on ChAT. This review outlines a new model for the regulation of cholinergic transmission at the level of the presynaptic terminal that is mediated by hierarchically‐regulated, multi‐site phosphorylation of ChAT.