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(Fps1p|GlpF|acute promyelocytic leukemia)
* Department of Biochemistry and Molecular Biology, Wayne State
University, School of Medicine, Detroit, MI 48201; and
Contributed by Peter Agre, March 7, 2002
Much is known about the transport of arsenite and antimonite
into microbes, but the identities of mammalian transport proteins are
unknown. The Saccharomyces cerevisiae FPS1 gene
encodes a membrane protein homologous to the bacterial aquaglyceroporin GlpF and to mammalian aquaglyceroporins AQP7 and AQP9. Fps1p mediates glycerol uptake and glycerol efflux in response to hypoosmotic shock.
Fps1p has been shown to facilitate uptake of the metalloids arsenite
and antimonite, and the Escherichia coli homolog, GlpF, facilitates the uptake and sensitivity to metalloid salts. In this
study, the ability of mammalian aquaglyceroporins AQP7 and AQP9 to
substitute for the yeast Fps1p was examined. The fps1
Cell Biology
Arsenite transport by mammalian aquaglyceroporins AQP7 and AQP9
,
, and
Departments of Biological Chemistry and Medicine, Johns
Hopkins University School of Medicine, Baltimore, MD 21205
strain of S. cerevisiae exhibits increased tolerance to
arsenite and antimonite compared to a wild-type strain. Introduction of a plasmid containing AQP9 reverses the metalloid tolerance of the
deletion strain. AQP7 was not expressed in yeast. The
fps1
cells exhibit reduced transport of
73As(III) or 125Sb(III), but uptake is enhanced
by expression of AQP9. Xenopus laevis oocytes
microinjected with either AQP7 or AQP9 cRNA exhibited increased
transport of 73As(III). These results suggest that AQP9 and
AQP7 may be a major routes of arsenite uptake into mammalian cells, an
observation potentially of large importance for understanding the
action of arsenite as a human toxin and carcinogen, as well as its
efficacy as a chemotherapeutic agent for acute promyelocytic leukemia.
To whom reprint requests should be addressed.
E-mail: brosen{at}med.wayne.edu.
www.pnas.org/cgi/doi/10.1073/pnas.092131899
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