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Journal of Bacteriology, July 2000, p. 3619-3625, Vol. 182, No. 13
Department of Pharmacology, Kobe University
School of Medicine, Kobe 650-0017,1
Research and Development Center, Fuso Pharmaceutical
Industries, Osaka 536-0025,2 and Faculty
of Health Science, Kobe University School of Medicine, Kobe
654-0142,3 Japan
Received 24 January 2000/Accepted 4 April 2000
Lithium is the drug of choice for the treatment of bipolar
affective disorder. The identification of an in vivo target of lithium
in fission yeast as a model organism may help in the understanding of
lithium therapy. For this purpose, we have isolated genes whose overexpression improved cell growth under high LiCl concentrations. Overexpression of tol1+, one of the isolated
genes, increased the tolerance of wild-type yeast cells for LiCl but
not for NaCl. tol1+ encodes a member of the
lithium-sensitive phosphomonoesterase protein family, and it exerts
dual enzymatic activities, 3'(2'),5'-bisphosphate nucleotidase and
inositol polyphosphate 1-phosphatase. tol1+
gene-disrupted cells required high concentrations of sulfite in the
medium for growth. Consistently, sulfite repressed the sulfate
assimilation pathway in fission yeast. However,
tol1+ gene-disrupted cells could not fully
recover from their growth defect and abnormal morphology even when the
medium was supplemented with sulfite, suggesting the possible
implication of inositol polyphosphate 1-phosphatase activity for cell
growth and morphology. Given the remarkable functional conservation of
the lithium-sensitive dual-specificity phosphomonoesterase between
fission yeast and higher-eukaryotic cells during evolution, it may
represent a likely in vivo target of lithium action across many species.
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Tol1, a Fission Yeast Phosphomonoesterase, Is an In Vivo Target
of Lithium, and Its Deletion Leads to Sulfite Auxotrophy

*
Corresponding author. Mailing address: Department of
Pharmacology, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. Phone: 81-78-382-5441. Fax:
81-78-382-5459. E-mail: tkuno{at}kobe-u.ac.jp.
Present address: Department of Pharmacology, College of Medicine,
University of the Philippines Manila, Manila 1000, Philippines.
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