Choline Acetyltransferase: Celebrating Its Fiftieth Year

Abstract

It is well known that the regulation of choline acetyltransferase (ChAT) activity under physiological and pathological conditions is important for the development and neuronal activities of cholinergic systems involved in many fundamental brain functions. This review focuses on recent progress in understanding the regulation of ChAT at the levels of both the protein and the mRNA. A deficiency in ChAT activity has been reported for neurodegenerative conditions such as Alzheimer's disease, amyotrophic lateral sclerosis, and schizophrenia. Although a major feature of ChAT regulation is likely to involve the spatial and temporal control of transcription, regulation of expression can also be at the level of RNA processing, transport/ translocation, turnover, or translation. In addition, there is increasing evidence that ChAT might be regulated at the posttranslational level by compartmentation and/or covalent modification, i.e., phosphorylation, as well as noncovalent modification (protein‐protein interaction, etc.). Synaptic activity and the state of neuronal transmission may also involve the regulation of ChAT at different levels via both positive and negative feedback loops, as was demonstrated in the characterization of two ChAT mutant Drosophila strains. Clearly, identification of cholinergic‐specific elements and the characterization of the trans‐acting factors that bind to them represent an important area of future research. Equally important is research on the mechanisms governing ChAT as an enzymatic entity. The future should be an exciting time during which we look forward to the elucidation of the cholinergic signal and its regulation as well as the determination of the three‐dimensional structure of the enzyme.

Thematic Review Series: Glycerolipids. Phosphatidylcholine and choline homeostasis

“…The conversion of choline to acetylcholine is catalyzed by choline acetyltransferase (69). Acetylcholine was the first neurotransmitter to be described and plays an important role in learning, memory, and sleep.…”

ELISA methods to measure cholinergic markers and nerve growth factor receptors in cortex, hippocampus, prefrontal cortex, and basal forebrain from rat brain

“…ChAT, VAChT, and HACT/CHT are cholinergic marker proteins, i.e., only neurons that release the neurotransmitter acetylcholine express ChAT, VAChT, and HACT/CHT (Arvidsson et al, 1997;Okuda and Haga, 2003;Wu and Hersh, 1994). ChAT activity forms acetylcholine from acetyl coenzyme A and choline (Wu and Hersh, 1994).…”

Evaluation of a Combined Therapeutic Regimen of 8-OH-DPAT and Environmental Enrichment after Experimental Traumatic Brain Injury

“…One possibility is that in addition to preventing cell death, the increased numbers of ChAT þ cells reflects an increase in the expression of ChAT protein within the surviving neurons. ChAT is necessary for the production of acetylcholine, and under normal conditions, levels of ChAT are in kinetic excess (Rylett and Schmidt, 1993;Wu and Hersh, 1994). However, following TBI, the levels of ChAT within the cholinergic neurons may decrease significantly and become rate-limiting for the production of acetylcholine.…”