Maciaszczyk-Dziubinska E , Wawrzycka D , Wysocki R .

	Figure 1. Pathways for arsenic uptake and detoxification in the yeast S.cerevisiae. In yeast cells uptake of As(III) is facilitated mainly via the aquaglyceroporin Fps1 but in the absence of glucose As(III) also enters the cell through the hexose permeases Hxt (Hxt1-Hxt17, Gal2). As(V) is taken up by the phosphate transporters (Pho), such as Pho84 and Pho87, followed by reduction to As(III) by the arsenate reductase Acr2 in the cytoplasm. Next, As(III) is transported out of the cell by the As(III)/H+ antiporter Acr3 against the concentration gradient or by the aquaglyceroporin Fps1, especially during As(V) exposure, when the internal concentration of As(III) is higher than the outside. In addition, As(III) is conjugated with glutathione (GSH) and sequestrated into the vacuole by the ABC transporters Ycf1 and Vmr1.
	Figure 2. Routes for arsenic transport in higher plants. In plant cells As(III) is accumulated through the aquaporins of Nodulin26-like intrinsic protein subfamily (NIPs) and plasma membrane intrinsic protein subfamily (PIPs), while As(V) uptake is catalyzed by the phosphate transporters (PHT1). In the cytoplasm As(V) is rapidly reduced to As(III) by the arsenate reductase ACR2/CDC25. Upon binding to phytochelatins (PCs), PC2-As(III) complexes are compartmentalized into the vacuole by two A. thaliana ABC transporters, ABCC1 and ABCC2. As(III) can also leak out of the plant root cell via the NIP and PIP channels down the concentration gradient to external medium. On the other hand, in rice the silicon transporter Lsi2 localizing to the proximal side of root cells extrudes As(III) to the xylem contributing to metalloid accumulation in shoots and grain.
	Figure 3. Summary of arsenic transport pathways in mammalian cells. As(V) uptake is mediated by the high-affinity phosphate transporter NaPiIIb. Next, As(V) is reduced to As(III) by CDC25 phosphatases/arsenate reductases. As(III) is transported into the mammalian cells via multiple pathways: the aquaglyceroporins (AQP3, AQP7, AQP9, AQP10), the glucose permeases (GLUT1, GLUT2, GLUT5) or the organic anion transporting polypeptides (OATPB, OATPC). The AQP9 and GLUT2 transporters are also responsible for the transport of methylated species of As(III) out of the cells. The ABC transporters from the ABCB (MDR1/P-gp) and ABCC (MRP1 and MRP2) subfamilies are the major pathways of As(III) extrusion. Both MRP1 and MRP2 are able to transport inorganic and monomethylated forms of As(III) conjugated with glutathione. In addition, MRP2 mediates efflux of seleno-bis(S-glutathionyl) arsinium ion. The exact form of As(III) recognized by MDR1/P-gp is uncertain but it is not glutathione-S-conjugate.

Aaltonen, Transmembrane topology of the Acr3 family arsenite transporter from Bacillus subtilis. 2008, Pubmed

Aaltonen, Transmembrane topology of the Acr3 family arsenite transporter from Bacillus subtilis. 2008, Pubmed
Abedin, Arsenic accumulation and metabolism in rice (Oryza sativa L.). 2002, Pubmed
Ali, Arsenite transport in plants. 2009, Pubmed
Allen, Extensive contribution of the multidrug transporters P-glycoprotein and Mrp1 to basal drug resistance. 2000, Pubmed
Beene, Pentavalent arsenate transport by zebrafish phosphate transporter NaPi-IIb1. 2011, Pubmed , Xenbase
Beese, Identification of positive regulators of the yeast fps1 glycerol channel. 2009, Pubmed
Bhattacharjee, Drug uptake and pharmacological modulation of drug sensitivity in leukemia by AQP9. 2004, Pubmed , Xenbase
Bhattacharjee, Aquaglyceroporins: ancient channels for metalloids. 2008, Pubmed
Bhattacharjee, Adventitious arsenate reductase activity of the catalytic domain of the human Cdc25B and Cdc25C phosphatases. 2010, Pubmed
Bienert, Metalloids: essential, beneficial or toxic? Major intrinsic proteins sort it out. 2008, Pubmed
Bienert, A subgroup of plant aquaporins facilitate the bi-directional diffusion of As(OH)3 and Sb(OH)3 across membranes. 2008, Pubmed
Bobrowicz, Isolation of three contiguous genes, ACR1, ACR2 and ACR3, involved in resistance to arsenic compounds in the yeast Saccharomyces cerevisiae. 1997, Pubmed
Brochu, Antimony uptake systems in the protozoan parasite Leishmania and accumulation differences in antimony-resistant parasites. 2003, Pubmed
Broeks, Homologues of the human multidrug resistance genes MRP and MDR contribute to heavy metal resistance in the soil nematode Caenorhabditis elegans. 1996, Pubmed
Bun-Ya, Putative GTP-binding protein, Gtr1, associated with the function of the Pho84 inorganic phosphate transporter in Saccharomyces cerevisiae. 1992, Pubmed
Bun-ya, Two new genes, PHO86 and PHO87, involved in inorganic phosphate uptake in Saccharomyces cerevisiae. 1996, Pubmed
Calatayud, In vitro study of transporters involved in intestinal absorption of inorganic arsenic. 2012, Pubmed
Callahan, Heavy metal resistance: a new role for P-glycoproteins in Leishmania. 1991, Pubmed
Carbrey, Reduced arsenic clearance and increased toxicity in aquaglyceroporin-9-null mice. 2009, Pubmed
Carew, Selenium-dependent and -independent transport of arsenic by the human multidrug resistance protein 2 (MRP2/ABCC2): implications for the mutual detoxification of arsenic and selenium. 2010, Pubmed
Carew, Monomethylarsenic diglutathione transport by the human multidrug resistance protein 1 (MRP1/ABCC1). 2011, Pubmed
Chappuis, Melarsoprol-free drug combinations for second-stage Gambian sleeping sickness: the way to go. 2007, Pubmed
Chin, Heat shock and arsenite increase expression of the multidrug resistance (MDR1) gene in human renal carcinoma cells. 1990, Pubmed
Coelho, Functional genetic identification of PRP1, an ABC transporter superfamily member conferring pentamidine resistance in Leishmania major. 2003, Pubmed
Coelho, Intracellular location of the ABC transporter PRP1 related to pentamidine resistance in Leishmania major. 2006, Pubmed
Cole, Pharmacological characterization of multidrug resistant MRP-transfected human tumor cells. 1994, Pubmed
Dhaoui, Gex1 is a yeast glutathione exchanger that interferes with pH and redox homeostasis. 2011, Pubmed
Di, Regulation of the arsenic-responsive transcription factor Yap8p involves the ubiquitin-proteasome pathway. 2007, Pubmed
Dilda, Arsenical-based cancer drugs. 2007, Pubmed
Drobná, Metabolism of arsenic in human liver: the role of membrane transporters. 2010, Pubmed
Duan, A CDC25 homologue from rice functions as an arsenate reductase. 2007, Pubmed
Duan, Expressing ScACR3 in rice enhanced arsenite efflux and reduced arsenic accumulation in rice grains. 2012, Pubmed
Ellis, A novel arsenate reductase from the arsenic hyperaccumulating fern Pteris vittata. 2006, Pubmed
Frézard, New delivery strategies for the old pentavalent antimonial drugs. 2010, Pubmed
Fu, Properties of arsenite efflux permeases (Acr3) from Alkaliphilus metalliredigens and Corynebacterium glutamicum. 2009, Pubmed
Garelick, Arsenic pollution sources. 2008, Pubmed
Ghosh, Pathways of As(III) detoxification in Saccharomyces cerevisiae. 1999, Pubmed
González, PHOSPHATE TRANSPORTER TRAFFIC FACILITATOR1 is a plant-specific SEC12-related protein that enables the endoplasmic reticulum exit of a high-affinity phosphate transporter in Arabidopsis. 2005, Pubmed
Gourbal, Drug uptake and modulation of drug resistance in Leishmania by an aquaglyceroporin. 2004, Pubmed
Guo, The assembly of metals chelation by thiols and vacuolar compartmentalization conferred increased tolerance to and accumulation of cadmium and arsenic in transgenic Arabidopsis thaliana. 2012, Pubmed
Hagenbuch, Organic anion transporting polypeptides of the OATP/ SLC21 family: phylogenetic classification as OATP/ SLCO superfamily, new nomenclature and molecular/functional properties. 2004, Pubmed
Hamdi, Arsenic transport by zebrafish aquaglyceroporins. 2009, Pubmed , Xenbase
Ilina, Characterization of the DNA-binding motif of the arsenic-responsive transcription factor Yap8p. 2008, Pubmed
Indriolo, A vacuolar arsenite transporter necessary for arsenic tolerance in the arsenic hyperaccumulating fern Pteris vittata is missing in flowering plants. 2010, Pubmed
Isayenkov, The Arabidopsis thaliana aquaglyceroporin AtNIP7;1 is a pathway for arsenite uptake. 2008, Pubmed
Ishibashi, Aquaporin water channels in mammals. 2009, Pubmed
Jiang, Trivalent arsenicals and glucose use different translocation pathways in mammalian GLUT1. 2010, Pubmed
Kala, The MRP2/cMOAT transporter and arsenic-glutathione complex formation are required for biliary excretion of arsenic. 2000, Pubmed
Kamiya, NIP1;1, an aquaporin homolog, determines the arsenite sensitivity of Arabidopsis thaliana. 2009, Pubmed , Xenbase
Kamiya, Arabidopsis NIP1;1 transports antimonite and determines antimonite sensitivity. 2009, Pubmed
Lee, Enhanced expression of multidrug resistance-associated protein 2 and reduced expression of aquaglyceroporin 3 in an arsenic-resistant human cell line. 2006, Pubmed
Leslie, Arsenic transport by the human multidrug resistance protein 1 (MRP1/ABCC1). Evidence that a tri-glutathione conjugate is required. 2004, Pubmed
Leslie, Arsenic-glutathione conjugate transport by the human multidrug resistance proteins (MRPs/ABCCs). 2012, Pubmed
Leung, Relationship of expression of aquaglyceroporin 9 with arsenic uptake and sensitivity in leukemia cells. 2007, Pubmed
Li, The rice aquaporin Lsi1 mediates uptake of methylated arsenic species. 2009, Pubmed , Xenbase
Liu, Arsenic trioxide uptake by hexose permeases in Saccharomyces cerevisiae. 2004, Pubmed
Liu, Methylarsonous acid transport by aquaglyceroporins. 2006, Pubmed
Liu, Arsenite transport by mammalian aquaglyceroporins AQP7 and AQP9. 2002, Pubmed , Xenbase
Liu, Multidrug-resistance mdr1a/1b double knockout mice are more sensitive than wild type mice to acute arsenic toxicity, with higher arsenic accumulation in tissues. 2002, Pubmed
Liu, Overexpression of glutathione S-transferase II and multidrug resistance transport proteins is associated with acquired tolerance to inorganic arsenic. 2001, Pubmed
Liu, Mammalian glucose permease GLUT1 facilitates transport of arsenic trioxide and methylarsonous acid. 2006, Pubmed , Xenbase
Liu, Arsenic trioxide uptake by human and rat aquaglyceroporins. 2004, Pubmed , Xenbase
Long, Molecular analysis and heavy metal detoxification of ABCC1/MRP1 in zebrafish. 2011, Pubmed
Long, MRP proteins as potential mediators of heavy metal resistance in zebrafish cells. 2011, Pubmed
Lu, Organic anion transporting polypeptide-C mediates arsenic uptake in HEK-293 cells. 2006, Pubmed
Légaré, The Leishmania ATP-binding cassette protein PGPA is an intracellular metal-thiol transporter ATPase. 2001, Pubmed
López-Maury, Arsenic sensing and resistance system in the cyanobacterium Synechocystis sp. strain PCC 6803. 2003, Pubmed
Ma, Transporters of arsenite in rice and their role in arsenic accumulation in rice grain. 2008, Pubmed , Xenbase
Ma, A silicon transporter in rice. 2006, Pubmed
Maciaszczyk, Arsenical resistance genes in Saccharomyces douglasii and other yeast species undergo rapid evolution involving genomic rearrangements and duplications. 2004, Pubmed
Maciaszczyk-Dziubinska, The yeast aquaglyceroporin Fps1p is a bidirectional arsenite channel. 2010, Pubmed
Maciaszczyk-Dziubinska, The yeast permease Acr3p is a dual arsenite and antimonite plasma membrane transporter. 2010, Pubmed
Maciaszczyk-Dziubinska, Acr3p is a plasma membrane antiporter that catalyzes As(III)/H(+) and Sb(III)/H(+) exchange in Saccharomyces cerevisiae. 2011, Pubmed
Mandal, Assessing aquaglyceroporin gene status and expression profile in antimony-susceptible and -resistant clinical isolates of Leishmania donovani from India. 2010, Pubmed
Mansour, The bile/arsenite/riboflavin transporter (BART) superfamily. 2007, Pubmed
Marquis, Modulation in aquaglyceroporin AQP1 gene transcript levels in drug-resistant Leishmania. 2005, Pubmed
Martinez, Arsenic exposure and the induction of human cancers. 2011, Pubmed
Maurel, Plant aquaporins: novel functions and regulation properties. 2007, Pubmed
McDermott, Pentavalent methylated arsenicals are substrates of human AQP9. 2010, Pubmed , Xenbase
Mendoza-Cózatl, Tonoplast-localized Abc2 transporter mediates phytochelatin accumulation in vacuoles and confers cadmium tolerance. 2010, Pubmed
Meng, As(III) and Sb(III) uptake by GlpF and efflux by ArsB in Escherichia coli. 2004, Pubmed
Mosa, Members of rice plasma membrane intrinsic proteins subfamily are involved in arsenite permeability and tolerance in plants. 2012, Pubmed , Xenbase
Mukhopadhyay, Purification and characterization of ACR2p, the Saccharomyces cerevisiae arsenate reductase. 2000, Pubmed
Ortiz, Transport of metal-binding peptides by HMT1, a fission yeast ABC-type vacuolar membrane protein. 1995, Pubmed
Ouellette, ABC transporters in Leishmania and their role in drug resistance. 1998, Pubmed
Paumi, ABC transporters in Saccharomyces cerevisiae and their interactors: new technology advances the biology of the ABCC (MRP) subfamily. 2009, Pubmed
Persson, Regulation of phosphate acquisition in Saccharomyces cerevisiae. 2003, Pubmed
Porquet, Structural evidence of the similarity of Sb(OH)3 and As(OH)3 with glycerol: implications for their uptake. 2007, Pubmed
Prévéral, A common highly conserved cadmium detoxification mechanism from bacteria to humans: heavy metal tolerance conferred by the ATP-binding cassette (ABC) transporter SpHMT1 requires glutathione but not metal-chelating phytochelatin peptides. 2009, Pubmed
Ramírez-Solís, Experimental and theoretical characterization of arsenite in water: insights into the coordination environment of As-O. 2004, Pubmed
Rappa, Evidence that the multidrug resistance protein (MRP) functions as a co-transporter of glutathione and natural product toxins. 1997, Pubmed
Rosen, Arsenic transport in prokaryotes and eukaryotic microbes. 2010, Pubmed
Sanders, Antimonite is accumulated by the glycerol facilitator GlpF in Escherichia coli. 1997, Pubmed
Sato, The ars operon in the skin element of Bacillus subtilis confers resistance to arsenate and arsenite. 1998, Pubmed
Schwartz, Detoxification of multiple heavy metals by a half-molecule ABC transporter, HMT-1, and coelomocytes of Caenorhabditis elegans. 2010, Pubmed
Sharom, The P-glycoprotein multidrug transporter. 2011, Pubmed
Shin, Phosphate transport in Arabidopsis: Pht1;1 and Pht1;4 play a major role in phosphate acquisition from both low- and high-phosphate environments. 2004, Pubmed
Slot, Mammalian multidrug-resistance proteins (MRPs). 2011, Pubmed
Song, Arsenic tolerance in Arabidopsis is mediated by two ABCC-type phytochelatin transporters. 2010, Pubmed
Sooksa-Nguan, Drosophila ABC transporter, DmHMT-1, confers tolerance to cadmium. DmHMT-1 and its yeast homolog, SpHMT-1, are not essential for vacuolar phytochelatin sequestration. 2009, Pubmed
Takano, The Arabidopsis major intrinsic protein NIP5;1 is essential for efficient boron uptake and plant development under boron limitation. 2006, Pubmed , Xenbase
Tamás, Fps1p controls the accumulation and release of the compatible solute glycerol in yeast osmoregulation. 1999, Pubmed
Thomas, Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals. 2007, Pubmed
Thorsen, The MAPK Hog1p modulates Fps1p-dependent arsenite uptake and tolerance in yeast. 2006, Pubmed
Tschan, Antimony uptake by Zea mays (L.) and Helianthus annuus (L.) from nutrient solution. 2008, Pubmed
Vatamaniuk, Mechanism of heavy metal ion activation of phytochelatin (PC) synthase: blocked thiols are sufficient for PC synthase-catalyzed transpeptidation of glutathione and related thiol peptides. 2000, Pubmed
Vatamaniuk, Worms take the 'phyto' out of 'phytochelatins'. 2002, Pubmed
Vernhet, Resistance of human multidrug resistance-associated protein 1-overexpressing lung tumor cells to the anticancer drug arsenic trioxide. 2001, Pubmed
Vernhet, Overexpression of the multidrug resistance-associated protein (MRP1) in human heavy metal-selected tumor cells. 1999, Pubmed
Vernhet, Differential sensitivities of MRP1-overexpressing lung tumor cells to cytotoxic metals. 2000, Pubmed
Villa-Bellosta, Arsenate transport by sodium/phosphate cotransporter type IIb. 2010, Pubmed , Xenbase
Villadangos, Efflux permease CgAcr3-1 of Corynebacterium glutamicum is an arsenite-specific antiporter. 2012, Pubmed
Wawrzycka, Vmr 1p is a novel vacuolar multidrug resistance ABC transporter in Saccharomyces cerevisiae. 2010, Pubmed
Wu, Investigating the contribution of the phosphate transport pathway to arsenic accumulation in rice. 2011, Pubmed
Wu, Membrane topology of the ArsB protein, the membrane subunit of an anion-translocating ATPase. 1992, Pubmed
Wysocki, How Saccharomyces cerevisiae copes with toxic metals and metalloids. 2010, Pubmed
Wysocki, The glycerol channel Fps1p mediates the uptake of arsenite and antimonite in Saccharomyces cerevisiae. 2001, Pubmed
Wysocki, Transcriptional activation of metalloid tolerance genes in Saccharomyces cerevisiae requires the AP-1-like proteins Yap1p and Yap8p. 2004, Pubmed
Wysocki, The Saccharomyces cerevisiae ACR3 gene encodes a putative membrane protein involved in arsenite transport. 1997, Pubmed
Xia, Investigation of the structure and function of a Shewanella oneidensis arsenical-resistance family transporter. 2008, Pubmed
Xie, Toxicokinetic and genomic analysis of chronic arsenic exposure in multidrug-resistance mdr1a/1b(-/-) double knockout mice. 2004, Pubmed
Yang, Novel pathway for arsenic detoxification in the legume symbiont Sinorhizobium meliloti. 2005, Pubmed
Yompakdee, A putative membrane protein, Pho88p, involved in inorganic phosphate transport in Saccharomyces cerevisiae. 1996, Pubmed
Zhao, The role of the rice aquaporin Lsi1 in arsenite efflux from roots. 2010, Pubmed , Xenbase
Zhou, Leishmania major LmACR2 is a pentavalent antimony reductase that confers sensitivity to the drug pentostam. 2004, Pubmed