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A model for dynamic regulation of choline acetyltransferase by phosphorylation
Author(s) -
Dobransky Tomas,
Rylett R. Jane
Publication year - 2005
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 - 10.1111/j.1471-4159.2005.03367.x
Subject(s) - choline acetyltransferase , cholinergic , phosphorylation , acetylcholine , cholinergic neuron , kinase , microbiology and biotechnology , neuroscience , neurotransmitter , biology , protein kinase a , biochemistry , endocrinology , central nervous system
Abstract 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 Ca 2+ /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.