Arsenite transport by mammalian aquaglyceroporins AQP7 and AQP9.
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 fps1Delta 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 fps1Delta cells exhibit reduced transport of (73)As(III) or (125)Sb(III), but uptake is enhanced by expression of AQP9. Xenopus laevis oocytes microinjected with either AQP7 or AQP9 cRNA exhibited increased transport of (73)As(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.
Liu
Zijuan
Z
Department of Biochemistry and Molecular Biology, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
Shen
Jian
J
Carbrey
Jennifer M
JM
Mukhopadhyay
Rita
R
Agre
Peter
P
Rosen
Barry P
BP
D000818:Animals; D020346:Aquaporins / Q000378:metabolism*; D018053:Arsenites / Q000378:metabolism*; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008954:Models, Biological; D010957:Plasmids / Q000378:metabolism; D018075:RNA, Complementary / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D013997:Time Factors; D014981:Xenopus
C114141:AQP7 protein, human; C109669:AQP9 protein, human; C491927:Aqp7 protein, mouse; C491638:Aqp9 protein, mouse; D020346:Aquaporins; D018053:Arsenites; D018076:DNA, Complementary; C093263:FPS1 protein, S cerevisiae; D005656:Fungal Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D018075:RNA, Complementary; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; C015001:arsenite