Aquaporins with anion/monocarboxylate permeability: mechanisms, relevance for pathogenâ€“host interactions

Rambow, Janis; Wu, Binghua; Rönfeldt, Deike; Beitz, Eric

doi:10.3389/fphar.2014.00199

Cited by 35 publications

(26 citation statements)

References 66 publications

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“…It has been widely accepted that members of the AQP family, including those from the NIP subfamily, transport noncharged molecules (25,26), although recent studies have suggested that some members of the AQP family could transport charged substrates (27,28). However, the major Al species at low pH (4.2) is the charged Al 3+ ion (29).…”

Section: Nip1;2 Facilitates Passive Bidirectional Aluminum Transport mentioning

confidence: 99%

NIP1;2 is a plasma membrane-localized transporter mediating aluminum uptake, translocation, and tolerance inArabidopsis

Wang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

134

133

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Members of the aquaporin (AQP) family have been suggested to transport aluminum (Al) in plants; however, the Al form transported by AQPs and the roles of AQPs in Al tolerance remain elusive. Here we report that NIP1;2, a plasma membrane-localized member of the Arabidopsis nodulin 26-like intrinsic protein (NIP) subfamily of the AQP family, facilitates Al-malate transport from the root cell wall into the root symplasm, with subsequent Al xylem loading and root-toshoot translocation, which are critical steps in an internal Al tolerance mechanism in Arabidopsis. We found that NIP1;2 transcripts are expressed mainly in the root tips, and that this expression is enhanced by Al but not by other metal stresses. Mutations in NIP1;2 lead to hyperaccumulation of toxic Al 3+ in the root cell wall, inhibition of root-to-shoot Al translocation, and a significant reduction in Al tolerance. NIP1;2 facilitates the transport of Al-malate, but not Al 3+ ions, in both yeast and Arabidopsis. We demonstrate that the formation of the Al-malate complex in the root tip apoplast is a prerequisite for NIP1;2-mediated Al removal from the root cell wall, and that this requires a functional root malate exudation system mediated by the Al-activated malate transporter, ALMT1. Taken together, these findings reveal a critical linkage between the previously identified Al exclusion mechanism based on root malate release and an internal Al tolerance mechanism identified here through the coordinated function of NIP1;2 and ALMT1, which is required for Al removal from the root cell wall, root-to-shoot Al translocation, and overall Al tolerance in Arabidopsis.aquaporin | nodulin 26-like protein | aluminum tolerance | organic acid exudation | malate

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Section: Nip1;2 Facilitates Passive Bidirectional Aluminum Transport mentioning

confidence: 99%

NIP1;2 is a plasma membrane-localized transporter mediating aluminum uptake, translocation, and tolerance inArabidopsis

Wang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

134

133

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“…an asparagine residue instead of an otherwise perfectly conserved glycine at a helix crossing point, which allows for slippery helix movements that widen the channel permitting passage of partially hydrated anions (12). The situation regarding the protonation state of weak acid substrates, such as organic monocarboxylates, is more complex (13). There are several reports on monocarboxylate permeability of AQPs, mainly for lactate/lactic acid, e.g.…”

mentioning

confidence: 99%

Electrostatic attraction of weak monoacid anions increases probability for protonation and passage through aquaporins

Rothert

Rönfeldt

Beitz

2017

Journal of Biological Chemistry

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A positive electrostatic field emanating from the center of the aquaporin (AQP) water and solute channel is responsible for the repulsion of cations. At the same time, however, a positive field will attract anions. In this regard, l-lactate/lactic acid permeability has been shown for various isoforms of the otherwise highly water and neutral substrate selective AQP family. The structural requirements rendering certain AQPs permeable for weak monoacids and the mechanism of conduction have remained unclear. Here, we show by profiling pH-dependent substrate permeability, measurements of media alkalization, and proton decoupling that AQP9 acts as a channel for the protonated, neutral monocarboxylic acid species. Intriguingly, the obtained permeability rates indicate an up to 10 times higher probability of passage via AQP9 than given by the fraction of the protonated acid substrate at a certain pH. We generated AQP9 point mutants showing that this effect is independent from properties of the channel interior but caused by the protein surface electrostatics. Monocarboxylic acid-conducting AQPs thus employ a mechanism similar to the family of formate-nitrite transporters for weak monoacids. On a more general basis, our data illustrate semiquantitatively the contribution of surface electrostatics to the interaction of charged molecule substrates or ligands with target proteins, such as channels, transporters, enzymes, or receptors.

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“…Lactate permeation by AQP9 has been previously reported (Tsukaguchi et al 1998; Tsukaguchi et al 1999a). Mechanisms of AQP9 anion transport have been discussed, and AQP9 is proposed to act as a channel for the protonated lactic acid form (Rambow et al 2014). Since humans have a large family of monocarboxylate transporters (MCTs) expressed in all tissues(Halestrap 2013), the physiological role of AQP9 in lactate transport is questionable.…”

Section: Discussionmentioning

confidence: 99%

Role of AQP9 in transport of monomethyselenic acid and selenite

et al. 2017

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AQP9 is an aquaglyceroporin with a very broad substrate spectrum. In addition to its orthodox nutrient substrates, AQP9 also transports multiple neutral and ionic arsenic species including arsenic trioxide, monomethylarsenous acid (MAsIII) and dimethylarsenic acid (DMAV). Here we discovered a new group of AQP9 substrates which include two clinical relevant selenium species. We showed that AQP9 efficiently transports monomethylselenic acid (MSeA) with a preference for acidic pH, which has been demonstrated in X. laevis oocyte following the overexpression of human AQP9. Specific inhibitors that dissipate transmembrane proton potential or change the transmembrane pH gradient, such as FCCP, valinomycin, and nigericin did not significantly inhibit MSeA uptake, suggesting MSeA transport is not proton coupled. AQP9 was also found to transport ionic selenite and lactate, with much less efficiency compared with MSeA transport. Selenite and lactate uptake via AQP9 is pH gradient dependent and inhibited by FCCP and nigericin, but not valinomycin. The selenite and lactate uptake via AQP9 can be inhibited by different lactate analogs, indicating that their translocation share similar mechanisms. AQP9 transport of MSeA, selenite and lactate is all inhibited by a previously identified AQP9 inhibitor, phloretin, and the AQP9 substrate AsIII. These newly identified AQP9 selenium substrates imply that AQP9 could play a significant role in MSeA uptake and possibly selenite uptake involved with cancer therapy under specific microenvironments.

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Aquaporins with anion/monocarboxylate permeability: mechanisms, relevance for pathogenâ€“host interactions

Cited by 35 publications

References 66 publications

NIP1;2 is a plasma membrane-localized transporter mediating aluminum uptake, translocation, and tolerance inArabidopsis

NIP1;2 is a plasma membrane-localized transporter mediating aluminum uptake, translocation, and tolerance inArabidopsis

Electrostatic attraction of weak monoacid anions increases probability for protonation and passage through aquaporins

Role of AQP9 in transport of monomethyselenic acid and selenite

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