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J Biol Chem, Vol. 274, Issue 27, 19417-19421, July 2, 1999
From the Department of Physiology, The University of Western
Ontario and the Neurodegenerative Diseases Group, The John P. Robarts
Research Institute, London, Ontario N6A 5C1, Canada
Choline acetyltransferase is the enzyme
catalyzing synthesis of the neurotransmitter acetylcholine in
cholinergic neurons. In human, transcripts encoding 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-kDa 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 protein is found in cytoplasm. Expression of site-directed and
deletion mutants 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 neurotransmitter-synthesizing enzyme that is localized to
the cell nucleus.
Nuclear Localization of the 82-kDa Form of Human Choline
Acetyltransferase
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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