Molecular Biology and Neurobiology of Choline Acetyltransferase

In the 45 years since the first description of choline acetyltransferase (ChAT; EC 2.3.1.6.), significant progress has been made in characterizing the molecular properties of this important neurotransmitter synthetic enzyme. We are now on the verge of understanding its genetic regulation and biological function(s). The Drosophila cDNA has been cloned, sequenced, and expressed in both a eucaryotic and a procaryotic system. The levels of ChAT specific mRNA have been determined during Drosophila development. Monoclonal and polyclonal antibodies have been produced to the enzyme from a variety of sources and used for biochemical and immunocytochemical studies. Two well characterized genetic systems have identified the ChAT gene and described a series of useful alleles. As a nervous system specific protein expressed only in the subset of neurons using acetylcholine as a neurotransmitter, ChAT is a good model for uncovering the processes and factors responsible for regulating genes involved in neurotransmitter phenotype selection and maintenance. Recent studies have described the purification of a cholinergic factor from muscle conditioned medium and indicated the potential importance of nerve growth factor (NGF) for regulating ChAT expression in the central nervous system. These factors, or ones remaining to be discovered, may be involved in the etiology or disease process of neurodegenerative nervous system disorders such as Alzheimer's disease.