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1.A.8 The Major Intrinsic Protein (MIP) Family

The Major Intrinsic Protein (MIP) of the human lens of the eye (Aqp0), after which the MIP family was named, represents about 60% of the protein in the lens cell. In the native form, it is an aquaporin, but during lens development, it becomes proteolytically truncated. The channel, which normally houses 6-9 water molecules, becomes constricted so only three remain, and these are trapped in a closed conformation (Gonen et al., 2004a,b). These truncated tetramers form intercellular adhesive junctions (head to head), yielding a crystalline array that mediates lens formation with cells tightly packed as required to form a clear lens (Gonen and Walz, 2006). Lipids crystallize with the protein (Gonen et al., 2005). Ion channel activity has been shown for Aquaporins 0, 1, and 6, Drosophila Big Brain and plant Nodulin-26 (Yool and Campbell, 2012).  Roles of aquaporins in human cancer have been reviewed (Pareek et al. 2013).

The MIP family is large and diverse, possessing over 100 members that all form transmembrane channels. These channel proteins function in water, small carbohydrate (e.g., glycerol), urea, NH3, CO2, H2O2 and ion transport by energy-independent mechanisms. For example, the glycerol channel, Fpslp of Saccharomyces cerevisiae mediates uptake of arsenite and antimonite (Wysocki et al., 2001). Ion permeability appears to occur through a pathway different than that used for water/glycerol transport and may involve a channel at the 4 subunit interface rather than the channels through the subunits (Saparov et al., 2001). MIP family members are found ubiquitously in bacteria, archaea and eukaryotes. Phylogenetic clustering of the proteins is largely according to phylum of the organisms of origin, but one to three clusters are observed for each phylogenetic kingdom (plants, animals, yeast, bacteria and archaea) (Park and Saier, 1996). One of the plant clusters includes only tonoplast (TIP) proteins, with another includes plasma membrane (PIP) proteins (see below).

The known aquaporins cluster loosely together as do the known glycerol facilitators. MIP family proteins are believed to form aqueous pores that selectively allow passive transport of their solute(s) across the membrane with minimal apparent recognition. Aquaporins selectively transport water (but not glycerol) while glycerol facilitators selectively transport glycerol but not water. Some aquaporins can transport NH3 and CO2. Glycerol facilitators function as solute nonspecific channels, and may transport glycerol, dihydroxyacetone, propanediol, urea and other small neutral molecules in physiologically important processes. Some members of the family, including the yeast Fps1 protein (TC #1.A.8.5.1) and tobacco NtTIPa (TC #1.A.8.10.2) may transport both water and small solutes.

Zardoya and Villalba (2001) have conducted phylogenetic analyses of the MIP family, analyzing 153 homologues. They divided the proteins into six major 'paralogous' groups: (1) GLPs, or glycerol-transporting channel proteins, which include mammalian AQP3, AQP7, and AQP9, several nematode paralogues, a yeast paralogue, and Escherichia coli GLP; (2) AQPs, or aquaporins, which include metazoan AQP0, AQP1, AQP2, AQP4, AQP5, and AQP6; (3) PIPs, or plasma membrane intrinsic proteins of plants, which include PIP1 and PIP2; (4) TIPs, or tonoplast intrinsic proteins of plants, which include αTIP, γTIP, and δTIP; (5) NODs, or nodulins of plants; and (6) AQP8s, or metazoan aquaporin 8 proteins. Of these groups, AQPs, PIPs, and TIPs cluster together as noted above.

In agreement with their divergent sequences, human AQP1-9 have very different physiological functions. They are involved in (1) nephrogenic diabetes insipidus, (2) brain water balance and hearing and (3) salivary secretion (Li and Verkman, 2001).  Bacterial homologues also have diverse functions.  Two proteins in E. coli function as water and glycerol transporters, respectively.  Lactobacillus plantarum has 6 homologues, some of which transport water, glycerol and dihydroxyacetone, and some which transporter these compounds as well as D,L-lactic acid (Bienert et al. 2013).

Several reports of MIP family proteins transporting ions may or may not be physiologically significant. For example, the influx of arsenite and antimonite via the Fps1 protein into yeast cells is well documented (Wysocki et al., 2001). Similarly, these compounds are taken up via aquaporins in Leishmania (Gourbal et al., 2004). Moreover, AQP6 of renal epithelia have been reported to transport anions at low pH (Yasui et al., 1999). Demonstration of the involvement of the cyanobacterial channel protein (TC #1.A.8.4.1) in copper homeostasis suggests that it may transport Cu2+. Finally, Yang et al. (2005) showed that arsenite exists the Mesorhizobium meliloti cell by downhill movement through AqpS (1.A.8.15.1). The physiological functions of many MIP family proteins are unknown.

MIP family channels consist of homotetramers (e.g., GlpF of E. coli; TC #1.A.8.1.1, AqpZ of E. coli; TC #1.A.8.3.1, and MIP or Aqp0 of Bos taurus; TC #1.A.8.8.1). Each subunit spans the membrane six times as putative α-helices and arose from a 3-spanner-encoding genetic element by a tandem, intragenic duplication event. The two halves of the proteins are therefore of opposite orientation in the membrane. However, a well-conserved region between TMSs 2 and 3 and TMSs 5 and 6 dip into the membrane, each loop forming a half TMS.

Several MIPs within all domains of life have been shown to facilitate the diffusion of reduced and non-charged species of the metalloids silicon, boron, arsenic and antimony (Bienert et al., 2008). Metalloids encompass a group of biologically important elements ranging from the essential to the highly toxic. Consequently, all organisms require efficient membrane transport systems to control the exchange of metalloids with the environment. Recent genetic evidence has demonstrated a crucial role for specific MIPs in metalloid homeostasis (Bienert et al., 2008).

The crystal structure of the glycerol facilitator of E. coli was solved at 2.2 Å resolution (Fu et al., 2000). Glycerol molecules line up in single file within the amphipathic channel. In the narrow selectivity filter of the channel, the glycerol alkyl backbone is wedged against a hydrophobic corner, and successive hydroxyl groups form hydrogen bonds with a pair of acceptor and donor atoms. The two conserved D-P-A motifs in the loops between TMSs 2 and 3 and TMSs 5 and 6 form the interface between the two duplicated halves of each subunit. Thus each half of the protein forms 3.5 TMSs surrounding the channel. The structure explains why GlpF is selectively permeable to straight chain carbohydrates, and why water and ions are excluded. Aquaporin-1 (AQP1) and the bacterial glycerol facilitator, GlpF can transport O2, CO2, NH3, glycerol, urea, and water to varying degrees. For small solutes permeating through AQP1, a remarkable anticorrelation between permeability and solute hydrophobicity was observed whereas the opposite trend was observed for permeation through the membrane (Hub and Groot, 2008). AQP1 is thus a selective filter for small polar solutes, whereas GlpF is highly permeable to small solutes and less permeable to larger solutes. 

Aquaporin-1 (Aqp1) from the human red blood cell has been solved by x-ray crystallography to 3.8 Å resolution (Murata et al., 2000). The aqueous pathway is lined with conserved hydrophobic residues that permit rapid water transport. Water selectivity is due to a constriction of the inner pore diameter to about 3 Å over the span of a single residue, superficially similar to that in the glycerol facilitator of E. coli.

AqpZ, a homotetramer (tAqpZ) of four water-conducting channels that facilitate rapid water movements across the plasma membrane of E. coli, has been solved to 3.2 Å resolution. All channel-lining residues in the four monomeric channels are found orientated in nearly identical positions with one marked exception at the narrowest channel constriction, where the side chain of a conserved Arg-189 adopts two distinct conformational orientations. In one of the four monomers, the guanidino group of Arg-189 points toward the periplasmic vestibule, opening up the constriction to accommodate the binding of a water molecule through a tridentate H-bond. In the other three monomers, the Arg-189 guanidino group bends over to form an H-bond with carbonyl oxygen of Thr-183 occluding the channel. Therefore, the tAqpZ structure reveals two distinct Arg-189 conformations associated with water permeation through the channel constrictions. Alternating between the two Arg-189 conformations disrupts continuous flow of water, thus regulating the open probability of the water pore. Further, the difference in Arg-189 displacements is correlated with a strong electron density found between the first transmembrane helices of two open channels, suggesting that the observed Arg-189 conformations are stabilized by asymmetrical subunit interactions in tAqpZ (Jiang et al., 2006).

The 3-D structures of the open and closed forms of plant aquaporins, PIP1 and PIP2, have been solved (Törnroth-Horsefield et al., 2006). In the closed conformation, loop D caps the channel from the cytoplasm and thereby occludes the pore. In the open conformation, loop D is displaced up to 16 Å, and this movement opens a hydrophobic gate blocking the channel entrance from the cytoplasm. These results reveal a molecular gating mechanism which appears conserved throughout all plant plasma membrane aquaporins. In plants it regulates water intake/export in response to water availability and cytoplasmic pH during anoxia (Törnroth-Horsefield et al., 2006).

The MIP superfamily includes three subfamilies: aquaporins, aquaglyceroporins and S-aquaporins. (1) The aquaporins (AQPs) are water selective. (2) The aquaglyceroporins are permeable to water, but also to other small uncharged molecules. (3) The third subfamily, with little conserved amino acid sequences around the NPA boxes, include 'superaquaporins' (S-aquaporins). 

The transport reaction for channel proteins of the MIP family is:

H2O (out) H2O (in) (e.g., aquaporins) or

 

solute (out) solute (in) (e.g., glycerol facilitators).

 

This family belongs to the: Major Intrinsic Protein (MIP) Superfamily.

References associated with 1.A.8 family:

Bienert, G.P., M.D. Schüssler, and T.P. Jahn. (2008). Metalloids: essential, beneficial or toxic? Major intrinsic proteins sort it out. Trends Biochem. Sci. 33: 20-26. 18068370
Amezcua-Romero JC., Pantoja O. and Vera-Estrella R. (2010). Ser123 is essential for the water channel activity of McPIP2;1 from Mesembryanthemum crystallinum. J Biol Chem. 285(22):16739-47. 20332086
Araya-Secchi, R., J.A. Garate, D.S. Holmes, and T. Perez-Acle. (2011). Molecular dynamics study of the archaeal aquaporin AqpM. BMC Genomics 12Suppl4: S8. 22369250
Ayadi, M., D. Cavez, N. Miled, F. Chaumont, and K. Masmoudi. (2011). Identification and characterization of two plasma membrane aquaporins in durum wheat (Triticum turgidum L. subsp. durum) and their role in abiotic stress tolerance. Plant Physiol. Biochem 49: 1029-1039. 21723739
Beese-Sims, S.E., J. Lee, and D.E. Levin. (2011). Yeast Fps1 glycerol facilitator functions as a homotetramer. Yeast 28: 815-819. 22030956
Beitz, E., S. Pavlovic-Djuranovic, M. Yasui, P. Agre, and J.E. Schultz. (2004). Molecular dissection of water and glycerol permeability of the aquaglyceroporin from Plasmodium falciparum by mutational analysis. Proc. Natl. Acad. Sci. USA 101: 1153-1158. 14734807
Bellati, J., K. Alleva, G. Soto, V. Vitali, C. Jozefkowicz, and G. Amodeo. (2010). Intracellular pH sensing is altered by plasma membrane PIP aquaporin co-expression. Plant Mol. Biol. 74: 105-118. 20593222
Berthaud, A., J. Manzi, J. Pérez, and S. Mangenot. (2012). Modeling detergent organization around aquaporin-0 using Small Angle X-ray Scattering. J. Am. Chem. Soc. [Epub: Ahead of Print] 22621369
Bertl, A., and R. Kaldenhoff. (2007). Function of a separate NH3-pore in Aquaporin TIP2;2 from wheat. FEBS Lett. 581: 5413-5417. 17967420
Bienert, G.P., A.L. Moller, K.A. Kristiansen, A. Schulz, I.M. Moller, J.K. Schjoerring, and T.P. Jahn. (2007). Specific aquaporins facilitate the diffusion of hydrogen peroxide across membranes. J. Biol. Chem. 282: 1183-1192. 17105724
Bienert, G.P., B. Desguin, F. Chaumont, and P. Hols. (2013). Channel-mediated lactic acid transport: a novel function for aquaglyceroporins in bacteria. Biochem. J. [Epub: Ahead of Print] 23799297
Buzhynskyy, N., J.F. Girmens, W. Faigle, S. Scheuring. (2007). Human cataract lens membrane at subnanometer resolution. J. Mol. Biol. 374: 162-169. 17920625
Calamita, G., B. Kempf, M. Bonhivers, W.R. Bishai, E. Bremer, and P. Agre. (1998). Regulation of the Escherichia coli water channel gene aqpZ. Proc. Natl. Acad. Sci. USA 95: 3627-3631. 9520416
Calamita. G. (2000). The Escherichia coli aquaporin-Z water channel. Mol. Microbiol. 37: 254-262. 10931322
Carbrey, J.M., D.A. Gorelick-Feldman, D. Kozono, J. Praetorius, S. Nielsen, and P. Agre. (2003). Aquaglyceroporin AQP9: solute permeation and metabolic control of expression in liver. Proc. Natl. Acad. Sci. USA 100: 2945-2950. 12594337
Carbrey, J.M., M. Bonhivers, J.D. Boeke, and P. Agre. (2001). Aquaporins in Saccharomyces: characterization of a second functional water channel protein. Proc. Natl. Acad. Sci. USA 98: 1000-1005. 11158584
Chiba, Y., N. Mitani, N. Yamaji, and J.F. Ma. (2009). HvLsi1 is a silicon influx transporter in barley. Plant J. 57: 810-818. 18980663
Choi, W.G., and D.M. Roberts. (2007). Arabidopsis NIP2;1, a major intrinsic protein transporter of lactic acid induced by anoxic stress. J. Biol. Chem. 282: 24209-24218. 17584741
Chrispeels, M.J. and C. Maurel. (1994). Aquaporins: the molecular basis of facilitated water movement through living plant cells? Plant Physiol. 105: 9-13. 7518091
Cui, Y. and D.A. Bastien. (2011). Water transport in human aquaporin-4: Molecular dynamics (MD) simulations. Biochem. Biophys. Res. Commun. 412: 654-659. 21856282
Dai, Y.H., B.R. Liu, H.J. Chiang, and H.J. Lee. (2011). Gene transport and expression by arginine-rich cell-penetrating peptides in Paramecium. Gene 489: 89-97. 21925248
Dean, R.M., R.L. Rivers, M.L. Zeide, and D.M. Roberts. (1999). Purification and functional reconstitution of soybean nodulin 26. An aquaporin with water and glycerol transport properties. Biochemistry 38: 347-353. 9890916
Deen, P.M.T. and C.H. van Os. (1998). Epithelial aquaporins. Curr. Opin. Cell Biol. 10: 435-442. 9719862
Di Giusto, G., P. Flamenco, V. Rivarola, J. Fernández, L. Melamud, P. Ford, and C. Capurro. (2012). Aquaporin 2-increased renal cell proliferation is associated with cell volume regulation. J. Cell. Biochem. 113: 3721-3729. 22786728
Dynowski, M., G. Schaaf, D. Loque, O. Moran, and U. Ludewig. (2008). Plant plasma membrane water channels conduct the signalling molecule H2O2. Biochem. J. 414: 53-61. 18462192
Engel, A., Y. Fujiyoshi, and P. Agre. (2000). The importance of aquaporin water channel protein structures. EMBO J. 19: 800-806. 10698922
Engel, A., Y. Fujiyoshi, T. Gonen, and T. Walz. (2008). Junction-forming aquaporins. Curr. Opin. Struct. Biol. 18: 229-235. 18194855
Fenton, R.A., H.B. Moeller, J.D. Hoffert, M.J. Yu, S. Nielsen, and M.A. Knepper. (2008). Acute regulation of aquaporin-2 phosphorylation at Ser-264 by vasopressin. Proc. Natl. Acad. Sci. U. S. A. 105: 3134-3139. 18287043
Figarella, K., M. Rawer, N.L. Uzcategui, B.K. Kubata, K. Lauber, F. Madeo, S. Wesselborg, and M. Duszenko. (2005). Prostaglandin D2 induces programmed cell death in Trypanosoma brucei bloodstream form. Cell Death Differ. 12: 335-346. 15678148
Figarella, K., N.L. Uzcategui, Y. Zhou, A. LeFurgey, M. Ouellette, H. Bhattacharjee, and R. Mukhopadhyay. (2007). Biochemical characterization of Leishmania major aquaglyceroporin LmAQP1: possible role in volume regulation and osmotaxis. Mol. Microbiol. 65: 1006-1017. 17640270
Froger, A., J.-P. Rolland, P. Bron, V. Lagrée, F. Le Cahérec, S. Deschamps, J.-F. Hubert, I. Pellerin, D. Thomas, and C. Delamarche. (2001). Functional characterization of a microbial aquaglyceroporin. Microbiology 147: 1129-1135. 11320116
Fu, D., A. Libson, L.J.W. Miercke, C. Weitzman, P. Nollert, J. Krucinski, and R.M. Stroud. (2000). Structure of a glycerol-conducting channel and the basis for its selectivity. Science 290: 481-486. 11039922
Geijer, C., D. Ahmadpour, M. Palmgren, C. Filipsson, D.M. Klein, M.J. Tamas, S. Hohmann, and K. Lindkvist-Petersson. (2012). Yeast aquaglyceroporins use the transmembrane core to restrict glycerol transport. J. Biol. Chem. [Epub: Ahead of Print] 22593571
Gerbeau, P., J. Güçlü, P. Ripoche, and C. Maurel. (1999). Aquaporin Nt-TIPa can account for the high permeability of tobacco cell vacuolar membrane to small neutral solutes. Plant J. 18: 577-587. 10417709
Gonen, T. and T. Walz. (2006). The structure of aquaporins. Q. Rev. Biophys. 39: 361-396. 17156589
Gonen, T., P. Sliz, J. Kistler, Y. Cheng, and T. Walz. (2004b). Aquaporin-0 membrane junctions reveal the structure of a closed water pore. Nature 429: 193-197. 15141214
Gonen, T., Y. Cheng, J. Kistler, and T. Walz. (2004a). Aquaporin-0 membrane junctions form upon proteolytic cleavage. J. Mol. Biol. 342: 1337-1345. 15351655
Gonen, T., Y. Cheng, P. Sliz, Y. Hiroaki, Y. Fujiyoshi, S.C. Harrison, and T. Walz. (2005). Lipid-protein interactions in double-layered two-dimensional AQP0 crystals. Nature 438: 633-638. Erratum in: Nature (2006) 441: 248. 16319884
Gourbal, B., N. Sonuc, H. Bhattacharjee, D. Legare, S. Sundar, M. Ouellette, B.P. Rosen, and R. Mukhopadhyay. (2004). Drug uptake and modulation of drug resistance in Leishmania by an aquaglyceroporin. J. Biol. Chem. 279: 31010-31017. 15138256
Hara-Chikuma, M., and A.S. Verkman. (2008). Prevention of skin tumorigenesis and impairment of epidermal cell proliferation by targeted aquaporin-3 gene disruption. Mol. Cell. Biol. 28: 326-332. 17967887
Hemley, S.J., L.E. Bilston, S. Cheng, J.N. Chan, and M.A. Stoodley. (2013). Aquaporin-4 expression in posttraumatic syringomyelia. J Neurotrauma. [Epub: Ahead of Print] 23441695
Herraiz, A., F. Chauvigné, J. Cerdà, X. Bellés, and M.D. Piulachs. (2011). Identification and functional characterization of an ovarian aquaporin from the cockroach Blattella germanica L. (Dictyoptera, Blattellidae). J Exp Biol 214: 3630-3638. 21993792
Heymann, J.B. and A. Engel. (2000). Structural clues in the sequences of the aquaporins. J. Mol. Biol. 295: 1039-1053. 10656809
Horsefield, R., K. Nordén, M. Fellert, A. Backmark, S. Törnroth-Horsefield, A.C. Terwisscha van Scheltinga, J. Kvassman, P. Kjellbom, U. Johanson, and R. Neutze. (2008). High-resolution x-ray structure of human aquaporin 5. Proc. Natl. Acad. Sci. USA 105: 13327-13332. 18768791
Hub, J.S. and B.L. de Groot. (2008). Mechanism of selectivity in aquaporins and aquaglyceroporins. Proc. Natl. Acad. Sci. USA 105: 1198-1203. 18202181
Hwang, J.H., S.R. Ellingson, and D.M. Roberts. (2010). Ammonia permeability of the soybean nodulin 26 channel. FEBS Lett. 584: 4339-4343. 20875821
Ikeda, M., E. Beitz, D. Kozono, W.B. Guggino, P. Agre, and M. Yasui. (2002). Characterization of aquaporin-6 as a nitrate channel in mammalian cells. Requirement of pore-lining residue threonine. J. Biol. Chem. 277: 39873-39879. 12177001
Isayenkov, S.V. and F.J. Maathuis. (2008). The Arabidopsis thaliana aquaglyceroporin AtNIP7;1 is a pathway for arsenite uptake. FEBS Lett. 582: 1625-1628. 18435919
Ishida, Y., T. Nagae, and M. Azuma. (2012). A Water-Specific Aquaporin is Expressed in the Olfactory Organs of the Blowfly, Phormia regina. J Chem Ecol. [Epub: Ahead of Print] 22767214
Ishikawa, F., S. Suga, T. Uemura, M.H. Sato, and M. Maeshima. (2005). Novel type aquaporin SIPs are mainly localized to the ER membrane and show cell-specific expression in Arabidopsis thaliana. FEBS Lett. 579: 5814-5820. 16223486
Jelen, S., P. Gena, J. Lebeck, A. Rojek, J. Praetorius, J. Frokiaer, R.A. Fenton, S. Nielsen, G. Calamita, and M. Rutzler. (2012). Aquaporin-9 and Urea Transporter-A gene deletions affect urea transmembrane passage in murine hepatocytes. Am. J. Physiol. Gastrointest Liver Physiol. [Epub: Ahead of Print] 23042941
Jiang, J., B.V. Daniels, and D. Fu. (2006). Crystal structure of AqpZ tetramer reveals two distinct Arg-189 conformations associated with water permeation through the narrowest constriction of the water-conducting channel. J. Biol. Chem. 281: 454-460. 16239219
Jung, H.J., J.Y. Park, H.S. Jeon, and T.H. Kwon. (2011). Aquaporin-5: a marker protein for proliferation and migration of human breast cancer cells. PLoS One 6: e28492. 22145049
Jungersted, J.M., J. Bomholt, N. Bajraktari, J.S. Hansen, D.A. Klærke, P.A. Pedersen, K. Hedfalk, K.H. Nielsen, T. Agner, and C. Hélix-Nielsen. (2013). In vivo studies of aquaporins 3 and 10 in human stratum corneum. Arch Dermatol Res. [Epub: Ahead of Print] 23677388
Kalluri, S.R., V. Rothhammer, O. Staszewski, R. Srivastava, F. Petermann, M. Prinz, B. Hemmer, and T. Korn. (2011). Functional characterization of aquaporin-4 specific T cells: towards a model for neuromyelitis optica. PLoS One 6: e16083. 21264240
Kikawada, T., A. Saito, Y. Kanamori, M. Fujita, K. Snigórska, M. Watanabe, and T. Okuda. (2008). Dehydration-inducible changes in expression of two aquaporins in the sleeping chironomid, Polypedilum vanderplanki. Biochim. Biophys. Acta. 1778: 514-520. 18082130
Kosinska Eriksson, U., G. Fischer, R. Friemann, G. Enkavi, E. Tajkhorshid, and R. Neutze. (2013). Subangstrom resolution X-ray structure details aquaporin-water interactions. Science 340: 1346-1349. 23766328
Kozono, D., X. Ding, I. Iwasaki, X. Meng, Y. Kamagata, P. Agre, and Y. Kitagawa. (2003). Functional expression and characterization of an archaeal aquaporin. AqpM from Methanothermobacter marburgensis. J. Biol. Chem. 278: 10649-10656. 12519768
Li, H., S. Lee, and B.K. Jap. (1997). Molecular design of aquaporin-1 water channel as revealed by electrocrystallography. Nature Struc. Biol. 4: 263-265. 9095192
Li, J. and A.S. Verkman. (2001). Impaired hearing in mice lacking aquaporin-4 water channels. J. Biol. Chem. 276: 31233-31237. 11406631
Li, R.Y., Y. Ago, W.J. Liu, N. Mitani, J. Feldmann, S.P. McGrath, J.F. Ma, and F.J. Zhao. (2009). The rice aquaporin Lsi1 mediates uptake of methylated arsenic species. Plant Physiol. 150: 2071-2080. 19542298
Li, T., W.G. Choi, I.S. Wallace, J. Baudry, and D.M. Roberts. (2011). Arabidopsis thaliana NIP7;1: an anther-specific boric acid transporter of the aquaporin superfamily regulated by an unusual tyrosine in helix 2 of the transport pore. Biochemistry 50: 6633-6641. 21710975
Liu, K., H. Tsujimoto, S.J. Cha, P. Agre, and J.L. Rasgon. (2011). Aquaporin water channel AgAQP1 in the malaria vector mosquito Anopheles gambiae during blood feeding and humidity adaptation. Proc. Natl. Acad. Sci. USA 108: 6062-6066. 21444767
Loqué, D., U. Ludewig, L. Yuan, and N. von Wirén. (2005). Tonoplast intrinsic proteins AtTIP2;1 and AtTIP2;3 facilitate NH3 transport into the vacuole. Plant Physiology 137: 671-680. 15665250
Lu, D.C., H. Zhang, Z. Zador, and A.S. Verkman. (2008). Impaired olfaction in mice lacking aquaporin-4 water channels. FASEB J. 22: 3216-3223. 18511552
Ma, J.F., K. Tamai, N. Yamaji, N. Mitani, S. Konishi, M. Katsuhara, M. Ishiguro, Y. Murata, and M. Yano. (2007b). A silicon transporter in rice. Nature 440: 688-691. 16572174
Ma, J.F., N. Yamaji, K. Tamai, and N. Mitani. (2007a). Genotypic difference in silicon uptake and expression of silicon transporter genes in rice. Plant Physiol. 145: 919-924. 17905867
Mahdieh, M., A. Mostajeran, T. Horie, and M. Katsuhara. (2008). Drought stress alters water relations and expression of PIP-type aquaporin genes in Nicotiana tabacum plants. Plant Cell Physiol. 49: 801-813. 18385163
Mallo, R.C. and Ashby, M.T. (2006). AqpZ-mediated water permeability in Escherichia coli measured by stopped-flow spectroscopy. J. Bacteriol. 188:820-822. 16385074
Mathew, L.G., E.M. Campbell, A.J. Yool, and J.A. Fabrick. (2011). Identification and characterization of functional aquaporin water channel protein from alimentary tract of whitefly, Bemisia tabaci. Insect Biochem Mol Biol 41: 178-190. 21146609
McDermott JR., Jiang X., Beene LC., Rosen BP. and Liu Z. (2010). Pentavalent methylated arsenicals are substrates of human AQP9. Biometals. 23(1):119-27. 19802720
Meng, Y.-L., Z. Liu, and B.P. Rosen. (2004). As(III) and Sb(III) uptake by GlpF and efflux by ArsB in Escherichia coli. J. Biol. Chem. 279: 18334-18341. 14970228
Mitani N., N. Yamaji, J.F. Ma. (2008). Characterization of substrate specificity of a rice silicon transporter, Lsi1. Pflugers Arch : . 18214526
Moe, S.E., J.G. Sorbo, R. Sogaard, T. Zeuthen, O. Petter Ottersen, and T. Holen. (2008). New isoforms of rat Aquaporin-4. Genomics 91: 367-377. 18255256
Mukhopadhyay, R., H. Bhattacharjee, and B.P. Rosen. (2013). Aquaglyceroporins: Generalized metalloid channels. Biochim. Biophys. Acta. [Epub: Ahead of Print] 24291688
Murata, K., K. Mitsuoka, T. Hirai, T. Walz, P. Agre, J.B. Heymann, A. Engel, and Y. Fujiyoshi. (2000). Structural determinants of water permeation through aquaporin-1. Science 407: 599-605.
Najafabadi, H.S., N. Torabi, and M. Chamankhah. (2008). Designing multiple degenerate primers via consecutive pairwise alignments. BMC Bioinformatics 9: 55. 18221562
Nakazawa, Y., M. Oka, A. Mitsuishi, M. Bando, and M. Takehana. (2011). Quantitative analysis of ascorbic acid permeability of aquaporin 0 in the lens. Biochem. Biophys. Res. Commun. 415: 125-130. 22020074
Navarro-Ródenas, A., J.M. Ruíz-Lozano, R. Kaldenhoff, and A. Morte. (2012). The aquaporin TcAQP1 of the desert truffle Terfezia claveryi is a membrane pore for water and CO(2) transport. Mol. Plant Microbe Interact. 25: 259-266. 22088195
Nemeth-Cahalan, K.L., K. Kalman, A. Froger, and J. E. Hall. (2007). Zinc Modulation of Water Permeability Reveals that Aquaporin 0 Functions as a Cooperative Tetramer. J. Gen. Physiol. 130(5):457-464. 17938229
Niemietz, C.M. and S.D. Tyerman. (2000). Channel-mediated permeation of ammonia gas through the peribacteroid membrane of soybean nodules. FEBS Lett. 465: 110-114. 10631315
Nozaki, K., D. Ishii, and K. Ishibashi. (2008). Intracellular aquaporins: clues for intracellular water transport? Pflugers Arch 456(4): 701-707. 18034355
Oliveira, R., F. Lages, M. Silva-Graça, and C. Lucas. (2003). Fps1p channel is the mediator of the major part of glycerol passive diffusion in Saccharomyces cerevisiae: artefacts and re-definitions. Biochim. Biophys. Acta. 1613: 57-71. 12832087
Pareek, G., V. Krishnamoorthy, and P. D' Silva. (2013). Molecular insights revealing interaction of Tim23 and channel subunits of presequence-translocase. Mol. Cell Biol. [Epub: Ahead of Print] 24061477
Park, J.H. and M.H. Saier, Jr. (1996). Phylogenetic characterization of the MIP family of transmembrane channel proteins. J. Membr. Biol. 153: 171-180. 8849412
Philip, B.N., A.J. Kiss, and R.E. Lee, Jr. (2011). The protective role of aquaporins in the freeze-tolerant insect Eurosta solidaginis: functional characterization and tissue abundance of EsAQP1. J Exp Biol 214: 848-857. 21307072
Pietrement, C., N. Da Silva, C. Silberstein, M. James, M. Marsolais, A. Van Hoek, D. Brown, N. Pastor-Soler, N. Ameen, R. Laprade, V. Ramesh, and S. Breton. (2008). Role of NHERF1, Cystic Fibrosis transmembrane conductance regulator, and cAMP in the regulation of aquaporin 9. J. Biol. Chem. 283: 2986-2996. 18055461
Pillitteri, L.J., N.L. Bogenschutz, and K.U. Torii. (2008). The bHLH protein, MUTE, controls differentiation of stomata and the hydathode pore in arabidopsis. Plant Cell Physiol. 49: 934-943. 18450784
Reizer, J., A. Reizer, and M.H. Saier, Jr. (1993). The MIP family of integral membrane channel proteins: sequence comparisons, evolutionary relationships, reconstructed pathway of evolution and proposed functional differentiation of the two repeated halves of the proteins. Crit. Rev. Biochem. Mol. Biol. 28: 235-257. 8325040
Saparov, S.M., D. Kozono, U. Rothe, P. Agre, and P. Pohl. (2001). Water and ion permeation of aquaporin-1 in planar lipid bilayers. Major differences in structural determinants and stoichiometry. J. Biol. Chem. 276: 31515-31520. 11410596
Saparov, S.M., K. Liu, P. Agre, and P. Pohl. (2007). Fast and selective ammonia transport by aquaporin-8. J. Biol. Chem. 282: 5296-5301. 17189259
Shukla, V.K. and M.J. Chrispeels. (1998). Aquaporins: their role and regulation in cellular water movement. NATO-ASI Series (subseries H). Cellular integration of signaling pathways in plant development, pp.11-22. Springer-Verlag.
Sidoux-Walter, F., N. Pettersson, and S. Hohmann. (2004). The Saccharomyces cerevisiae aquaporin Aqy1 is involved in sporulation. Proc. Natl. Acad. Sci. USA 101: 17422-17427. 15583134
Soria LR., Fanelli E., Altamura N., Svelto M., Marinelli RA. and Calamita G. (2010). Aquaporin-8-facilitated mitochondrial ammonia transport. Biochem Biophys Res Commun. 393(2):217-21. 20132793
Soto, G., K. Alleva, M.A. Mazzella, G. Amodeo, and J.P. Muschietti. (2008). AtTIP1;3 and AtTIP5;1, the only highly expressed Arabidopsis pollen-specific aquaporins, transport water and urea. FEBS Lett. 582: 4077-4082. 19022253
Soto, G., R. Fox, N. Ayub, K. Alleva, F. Guaimas, E.J. Erijman, A. Mazzella, G. Amodeo, and J. Muschietti. (2010). TIP5;1 is an aquaporin specifically targeted to pollen mitochondria and is probably involved in nitrogen remobilization in Arabidopsis thaliana. Plant J. 64: 1038-1047. 21143683
Suzuki, H., K. Nishikawa, Y. Hiroaki, and Y. Fujiyoshi. (2008). Formation of aquaporin-4 arrays is inhibited by palmitoylation of N-terminal cysteine residues. Biochim. Biophys. Acta. 1778(4): 1181-1189. 18179769
Törnroth-Horsefield, S., Y. Wang, K. Hedfalk, U. Johanson, M. Karlsson, E. Tajkhorshid, R. Neutze, and P. Kjellbom. (2006). Structural mechanism of plant aquaporin gating. Nature 439: 688-694. 16340961
Takano, J., M. Wada, U. Ludewig, G. Schaaf, N. von Wirén, and T. Fujiwara. (2006). The Arabidopsis major intrinsic protein NIP5;1 is essential for efficient boron uptake and plant development under boron limitation. The Plant Cell 18: 1498-1509. 16679457
Tani, K., T. Mitsuma, Y. Hiroaki, A. Kamegawa, K. Nishikawa, Y. Tanimura, and Y. Fujiyoshi. (2009). Mechanism of aquaporin-4's fast and highly selective water conduction and proton exclusion. J. Mol. Biol. 389: 694-706. 19406128
Uehlein, N., B. Otto, D.T. Hanson, M. Fischer, N. McDowell, and R. Kaldenhoff. (2008). Function of Nicotiana tabacum Aquaporins as Chloroplast Gas Pores Challenges the Concept of Membrane CO2 Permeability. Plant Cell 20: 648-657. 18349152
Uehlein, N., C. Lovisolo, F. Siefritz, and R. Kaldenhoff. (2003). The tobacco aquaporin NtAQP1 is a membrane CO2 pore with physiological functions. Nature (in press). 14520414
Uzcategui, N.L., A. Szallies, S. Pavlovic-Djuranovic, M. Palmada, K. Figarella, C. Boehmer, F. Lang, E. Beitz, and M. Duszenko. (2004). Cloning, heterologous expression, and characterization of three aquaglyceroporins from Trypanosoma brucei. J. Biol. Chem. 279: 42669-42676. 15294911
Verdoucq, L., A. Grondin, and C. Maurel. (2008). Structure-function analysis of plant aquaporin AtPIP2;1 gating by divalent cations and protons. Biochem. J. 415: 409-416. 18637793
Viadiu, H., T. Gonen, and T. Walz. (2007). Projection map of aquaporin-9 at 7 Å resolution. J. Mol. Biol. 367: 80-88. 17239399
Wysocki, R., C.C. Chéry, D. Wawrzycka, M. Van Hulle, R. Cornelis, J.M. Thevelein, and M.J. Tamás. (2001). The glycerol channel Fps1p mediates the uptake of arsenite and antimonite in Saccharomyces cerevisiae. Mol. Microbiol. 40: 1391-1401. 11442837
Yang, B., Z. Zador, and A.S. Verkman. (2008). Glial cell aquaporin-4 overexpression in transgenic mice accelerates cytotoxic brain swelling. J. Biol. Chem. 283: 15280-15286. 18375385
Yang, G., G. Zhang, Q. Wu, and J. Zhao. (2011). A novel mutation in the MIP gene is associated with autosomal dominant congenital nuclear cataract in a Chinese family. Mol Vis 17: 1320-1323. 21647270
Yang, H.-C., J. Cheng, T.M. Finan, B.P. Rosen, and H. Bhattacharjee. (2005). Novel pathway for arsenic detoxification in the legume symbiont Sinorhizobium meliloti. J. Bacteriol. 187: 6991-6997. 16199569
Yasui, M., A. Hazama, T.-H. Kwon, S. Nielsen, W.B. Guggino, and P. Agre. (1999). Rapid gating and anion permeability of an intracellular aquaporin. Nature 402: 184-187. 10647010
Yool, A.J. (2007). Dominant-negative suppression of big brain ion channel activity by mutation of a conserved glutamate in the first transmembrane domain. Gene Expr. 13: 329-337. 17708419
Yool, A.J. and E.M. Campbell. (2012). Structure, function and translational relevance of aquaporin dual water and ion channels. Mol Aspects Med. [Epub: Ahead of Print] 22342689
Yu, X.S., X. Yin, E.M. Lafer, and J.X. Jiang. (2005). Developmental regulation of the direct interaction between the intracellular loop of connexin 45.6 and the C terminus of major intrinsic protein (aquaporin-0). J. Biol. Chem. 280: 22081-22090. 15802270
Zardoya, R. and S. Villalba. (2001). A phylogenetic framework for the aquaporin family in eukaryotes. J. Mol. Evol. 52: 391-404. 11443343
Zeuthen T., B. Wu, S. Pavlovic-Djuranovic, L.M. Holm, N.L. Uzcategui, M. Duszenko, J.F. Kun, J.E. Schultz, E. Beitz. (2006). Ammonia permeability of the aquaglyceroporins from Plasmodium falciparum, Toxoplasma gondii and Trypansoma brucei. Mol. Microbiol. 61: 1598-1608. 16889642
Zhang, H. and A.S. Verkman. (2010). Aquaporin-1 tunes pain perception by interaction with Na(v)1.8 Na+ channels in dorsal root ganglion neurons. J. Biol. Chem. 285: 5896-5906. 20018876
Zhao, X.Q., N. Mitani, N. Yamaji, R.F. Shen, and J.F. Ma. (2010). Involvement of silicon influx transporter OsNIP2;1 in selenite uptake in rice. Plant Physiol. 153: 1871-1877. 20498338