Nuclear localization of the 82-kDa form of human choline acetyltransferase

Choline acetyltransferase is the enzyme catalyzing synthesis of the neurotr ansmitter acetylcholine in cholinergic neurons. In human, transcripts encod ing two forms of the enzyme with apparent molecular masses of 69 and 82 kDa are found in brain and spinal cord; the 82-kDa form differs from the 69-kD a enzyme only in terms of a 118-amino acid extension on its amino terminus. Using green fluorescent protein-tagged choline acetyltransferase, we show that the 82-kDa enzyme is targeted to nuclei of cells, whereas the 69-kDa p rotein is found in cytoplasm. Expression of site-directed and deletion muta nts of the 82-kDa isoform reveals that the extended amino terminus contains a nuclear localization signal in the first nine amino acids which targets the protein to nucleus. This represents the first report of a neurotransmit ter-synthesizing enzyme that is localized to the cell nucleus.