CHOLINE-ACETYLTRANSFERASE - CELEBRATING ITS 50TH YEAR

It is well known that the regulation of choline acetyltransferase (ChA T) activity under physiological and pathological conditions is importa nt for the development and neuronal activities of cholinergic systems involved in many fundamental brain functions. This review focuses on r ecent progress in understanding the regulation of ChAT at the levels o f both the protein and the mRNA. A deficiency in ChAT activity has bee n reported for neurodegenerative conditions such as Alzheimer's diseas e, amyotrophic lateral sclerosis, and schizophrenia. Although a major feature of ChAT regulation is likely to involve the spatial and tempor al control of transcription, regulation of expression can also be at t he level of RNA processing, transport/translocation, turnover, or tran slation. In addition, there is increasing evidence that ChAT might be regulated at the posttranslational level by compartmentation and/or co valent modification, i.e., phosphorylation, as well as noncovalent mod ification (protein-protein interaction, etc.). Synaptic activity and t he state of neuronal transmission may also involve the regulation of C hAT at different levels via both positive and negative feedback loops, as was demonstrated in the characterization of two ChAT mutant Drosop hila strains. Clearly, identification of cholinergic-specific elements and the characterization of the trans-acting factors that bind to the m 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 t he determination of the three-dimensional structure of the enzyme.