Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Filters applied. Clear all
, 99 (9), 6053-8

Arsenite Transport by Mammalian Aquaglyceroporins AQP7 and AQP9

Affiliations

Arsenite Transport by Mammalian Aquaglyceroporins AQP7 and AQP9

Zijuan Liu et al. Proc Natl Acad Sci U S A.

Abstract

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.

Figures

Figure 1
Figure 1
Expression of AQP9 in membranes of S. cerevisiae. Membranes were prepared from cells of strain HD9 or HD9 pAQP9 grown in the absence or presence of 2% galactose, as indicated. Membrane proteins were separated by SDS/PAGE and immunoblotted with anti-AQP9 as described in Materials and Methods.
Figure 2
Figure 2
AQP9 functionally complements the metalloid sensitivity of S. cerevisiae fps1Δ. Growth was measured in liquid SD minimal medium with 2% galactose (or, if repressed, glucose) in the presence of the indicated concentrations of sodium arsenite (A), potassium antimonyl tartrate (B), sodium arsenate (C), or cadmium chloride (D). Strains were: ■, MG102 (acr3Δ ycf1Δ); ○, HD9 (fps1Δ acr3Δ ycf1Δ) pYES3; ●, HD9 pAQP7 (induced); ▾, HD9 pAQP9 (induced); and ▿, HD9 pAQP9 (repressed).
Figure 3
Figure 3
AQP9 facilitates uptake of 73As(OH)3 and 125Sb(OH)3. (A) Transport of 73As(OH)3. (B) Inhibition of 73As(OH)3 uptake by glycerol. (C) Transport of 125Sb(OH)3. Strains were: ●, HD9 pYES3; ○, HD9 pAQP9; ▾, HD9 pAQP7; ▿, MG102; and ■, HD9 pAQP9 + 0.2 M glycerol.
Figure 4
Figure 4
73As(OH)3 permeability in Xenopus oocytes expressing AQP7 or AQP9. Oocyte transport of 73As(OH)3 was assayed for 90 sec as described in Materials and Methods. Each bar represents the average of three assays. Oocytes were injected with H2O, AQP7 cRNA, or AQP9 cRNA.
Figure 5
Figure 5
Metalloid transporters in prokaryotes and eukaryotes. The model shows a comparison of arsenite transport pathways in E. coli (A), S. cerevisiae (B), and a generalized mammalian cell (C). In each of three, arsenite uptake is facilitated by an aquaglyceroporin: the bacterial GlpF, the yeast Fps1p, or the mammalian AQP7 or AQP9. In E. coli, arsenite is extruded from the cytosol by the ArsAB pump. In yeast, arsenite extrusion from the cytosol is catalyzed by Acr3p or into the vacuole by the ATP-coupled Ycf1p pump as As(GS)3. In mammalian cells, various isoforms of the multidrug resistance associate protein (MRP), a Ycf1p homolog, pump out As(GS)3.

Similar articles

See all similar articles

Cited by 109 articles

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources

Feedback