"Aquaporins: Channels for the Molecule Of

Home , Aquaporin, Porin (protein)

Aquaporins: Channels for Advanced article Article Contents the Molecule of Life • Introduction • A Discovery Well Worth a Nobel Prize Uwe G Hacke, University of Alberta, Edmonton, Canada • Structure, Permeation and Substrate Speciﬁcity Joan Laur, University of Alberta, Edmonton, Canada • Regulation • Roles of Aquaporins in Different Life Forms • Future Directions • Acknowledgements

Online posting date: 15th February 2016

Liquid water has unique properties that make it The aquaporin protein family is ancient, and aquaporins can be a universal solvent. Water is an essential compo- found in a wide range of organisms, from unicellular bacteria nent of almost all physiological and biochemical to giant Sequoia trees. All aquaporins are recognised by shared, reactions; therefore, its presence is required every- conserved structures. The structure of the channels is important because it determines which molecules can pass, which are where within an organism. The circulatory systems excluded and at which rate molecules can move through the pores. of animals and the vascular system of plants move ﬂuids over long distances. In the tallest trees, water moves across a height gradient of 100 m or more, A Discovery Well Worth a Nobel thereby connecting roots and distant leaves. On a cellular and tissue level, water movement is facili- Prize tated by intrinsic membrane proteins called aqua- Transmembrane water flow was long believed to depend entirely porins. These water channels are found in all life on the permeability of the lipid bilayer and its composition. But forms. Aquaporins have been mostly studied in the high water permeability of certain membranes could not be mammals and plants, where water channels play fully explained until Peter Agre’s group (Smith and Agre, 1991; important physiological roles. This article gives an Agre et al., 1993) isolated and characterised the first human aqua- overview of the discovery, structure and regulation porin, CHIP28, later renamed AQP1. For decades, people have of aquaporins. Their roles in different life forms are speculated on the existence of microscopic pores that facilitate discussed. movement of molecules like water across biological membranes (Stein and Danielli, 1956). Rapid water flux was observed in toad bladders, mammalian kidneys and red blood cells. It was also found that high rates of water movement could be blocked in Introduction a reversible way by cytotoxic mercury reagents, suggesting the protein nature of what was later called aquaporins (Macey and While the lipid bilayer allows the slow diffusion of water Farmer, 1970; Macey, 1984). Finally, Wade et al. (1981) formu- molecules (see also: Lipid Bilayers), only the presence of lated the membrane shuttle hypothesis based on observations of a dedicated water channels can explain substantial water flow concomitant increase in cell permeability and the massive reloca- rates across some cell or subcellular membranes. Aquaporins are tion of protein aggregates from intracellular vesicles to the plasma integral membrane transport proteins, and they facilitate water membrane. What was the molecular identity of those proteins? movement in cells, tissues and entire organisms. The proper dis- It was also in the 1980s that Agre started working on the Rh tribution of the most abundant molecule in cells and living tissues blood group antigens. In the early years, his team had isolated is fundamental to life. In addition to water, certain aquaporins two membrane proteins of 32 and 28 kDa from red blood cells. also facilitate the transport of small solutes such as glycerol and The 28 kDa protein was found in spectacular quantity: 200 000 perhaps even gases like carbon dioxide. Molecules move through copies per red blood cell (Agre, 2004). The partial analysis of its the channels in response to osmotic/concentration gradients. sequence showed its close relation to proteins found in the kidney, eye lens, brain cells and also bacteria and plants; and several features suggested it was a membrane channel. The protein, tem- eLS subject area: Plant Science porarily named CHIP28 (for channel-like integral protein of 28 How to cite: kDa), was the subject of many discussions; but finally it was sug- Hacke, Uwe G and Laur, Joan (February 2016) Aquaporins: gested that it might be a water channel (Carbrey and Agre, 2009). Channels for the Molecule of Life. In: eLS. John Wiley & Sons, This hypothesis was soon tested by expressing CHIP28 in frog Ltd: Chichester. oocytes. This was a useful experiment, because oocytes nor- DOI: 10.1002/9780470015902.a0001289.pub2 mally show low water permeability. Oocytes expressing CHIP28

Control

CHIP28 sequence cRNA

Test

Xenopus Oocytes

Figure 1 Expression of CHIP28 water channel activity in Xenopus oocytes. Oocytes obtained from female Xenopus are injected with in vitro transcribed RNA of CHIP28. After a period of incubation, the water permeability of test oocytes expressing the protein and of control oocytes is tested in distilledwater. Almost immediately, ‘the test oocytes were highly permeable to water and exploded like popcorn’ (Agre, 2004). immediately swelled and exploded when transferred in distilled the answer is ‘no’; exceptionally high flow rates are possible water (Figure 1). Permeability to water was drastically increased. because of fine-tuned interactions between water molecules and The first water channel protein had just been functionally charac- the molecules forming the channel (Kozono et al., 2002; Eriksson terised ‘following the well-known scientific approach known as et al., 2013). sheer blind luck’ (Agre, 2004) and years of hard work. Aside from the central NPA constriction, aquaporins contain an outer constriction. This aromatic/arginine (ar/R) constriction region creates the narrowest section of the channel and constitutes Structure, Permeation a major checkpoint for solute permeability (Figure 2,dashed and Substrate Speciﬁcity ellipse). By mutating the ar/R filter, Beitz et al.(2006)were able to modify the water selectivity of AQP1 to allow urea, Aquaporins belong to the highly conserved major intrinsic protein ammonia and glycerol permeation. In aquaglyceroporins, the (MIP) super family (Danielson and Johanson, 2010). MIPs exist ar/R constriction region is wider than in orthodox water pores, as tetramers. Each subunit is behaving as a single aqueous pore. allowing the passage of larger molecules such as glycerol. Subunits share the same hourglass structure consisting of six transmembrane domains connected by several loops (Figure 2). Two of these loops fold back into the membrane and overlap. Regulation The overlapping loops each contain the conserved signature motif asparagine, proline, alanine (NPA). Located in the narrow centre Some aquaporins contain an additional energy barrier to water of the pore, the NPA region represents a key feature for water permeation, which allows these channels to be opened or permeation. The centre of water-selective pores has a minimum closed. In the spinach aquaporin SoPIP2;1, the phosphorylated diameter of 2.8 Å, almost matching the diameter of a water status of highly conserved amino acids, Ser115 and Ser274, molecule (Kozono et al., 2002). This means that water molecules controls the open/close conformation (gating) of the channel move through the centre of each pore in single-file configuration. (Törnroth-Horsefield et al., 2006). Such modifications, and also The water molecule passing the NPA motifs undergoes a transient the changes in pH, osmolarity and membrane tension, may lead reorientation as it forms hydrogen bonds between its oxygen and to the physical obstruction of the channel (Hedfalk et al., 2006). the partial positive charges of pore-lining asparagine residues. Other than gating, two other major modes of aquaporin regu- As a result of this and other features of the channel, protons are lation have been actively investigated: modification of their sub- unable to permeate the pores. The conserved NPA motifs’ partial cellular localisation and changes in gene expression. The shut- charges also play a key role in enhancing flow rates through the tle hypothesis (Wade et al., 1981), for instance, introduced the channel (Farimani et al., 2014). idea of water channel trafficking as a regulation strategy. The Despite the fact that water channels are only slightly wider than vasopressin-induced relocation of AQP2 that was observed in the water molecules that pass through them, they are enormously kidney cells is still intensively studied (Nedvetsky et al., 2009), efficient. Computer simulations suggest that a single water chan- and several other examples of protein transfer to the membrane nel allows the passive passage of more than one billion water have been reported (Ishikawa et al., 1999; Vera-Estrella et al., molecules per second; this is considerably faster than transport 2004; Boursiac et al., 2008;Luuet al., 2012). in some ion channels. With such extraordinary permeation rates, Another strategy to alter the number of proteins present in aquaporins are ideal channels to distribute water within organs or the membrane is to modify the level of gene expression, an tissues. The channels have to be narrow to be selective, but should approach used in the field of plant biotechnology in an effort this not come at the cost of slowing down transport? Apparently, to improve traits like drought resistance (Martre et al., 2002;

Extracellular side

HE H2H H4 H3

ar/R filter

NPA signature motifs

H5 H1 HB

N C Intracellular side

Figure 2 All aquaporin proteins share a common hourglass structure. They are composed of six transmembrane helices (H1–H6) connected by five loops (LA–LE); both N-andC-termini are located on the cytoplasmic side of the membrane. Two short helical domains (HB and HE) of LB and LE form a seventh ‘broken’ helix; they both contain a signature motif NPA (asparagine, proline, alanine) located in the middle of the pore. The aromatic/arginine constriction site (ar/R) is located closer to the extracellular side. Near the constriction sites, water molecules move in single-file configuration.

Guo et al., 2006; Zhang et al., 2013). Agreement of protein Aquaporins in microorganisms and fungi abundance and transcription levels has been described in plants (Laur and Hacke, 2013, 2014a) and mammals (Carbrey et al., The presence of aquaporin genes among microorganisms varies 2003). Adjustments in gene expression likely facilitate responses widely (Tanghe et al., 2006). While the number of aquaporin to changing environments or developmental factors. genes can range from one in several archaea, bacteria or yeast species to five in some filamentous fungi, numerous microorganisms appear to simply lack water channel proteins (Pettersson Roles of Aquaporins in Different et al., 2005). Aquaporin-deletion mutants did not show a con- spicuous phenotype. This and the absence of aquaporins in many Life Forms microbes may be related to the small size of individual microbial cells. There may be no need for enhanced water permeability, While the general function of aquaporins is to guide water move- although alternative explanations cannot be ruled out and remain ment within tissues, organs and entire organisms, the role of to be explored. Remarkably, aquaporins seem to protect microbial specific isoforms may vary depending on when and where they cells from the negative effects of rapid freezing (Tanghe et al., are expressed in an organism. Local protein malfunction has been 2002, 2006). Microbial aquaporins may enhance water transport linked with severe pathological disorders such as lens cataract at low temperatures when cell membranes become less fluid, and (Shiels and Bassnett, 1996)ordiabetes(Deenet al., 1994). Aqua- they may transport other molecules besides water such as the cry- porins also play important physiological roles in plant water oprotectant glycerol. relations. Many of these roles are not obvious during ‘normal’ circumstances, but may be most significant when plants are Aquaporins in animals stressed and exposed to quickly changing environmental condi- tions. The ubiquity of aquaporins in different life forms has also Perhaps surprisingly, only few invertebrate aquaporins have been been explained in the context of the sensor hypothesis, which characterised to date (Tomkowiak and Pienkowska, 2010). The proposes osmotic and turgor gradient-sensing functions for aqua- limited water reserves of insects can be easily depleted; hence, porins (Hill et al., 2004). the regulation of water uptake and loss is a major issue for insects

(Tsujimoto et al., 2013). Considering the enormous variety of species and physiological adaptations within the insects group alone, it will be interesting to learn about the multiple functions of aquaporins in invertebrates. For instance, it was recently suggested that the aquaporin AgAQP1 may play roles associated with mating as well as water homeostasis in the malaria vector F Anopheles gambiae (Tsujimoto et al., 2013). In fish and amphibians, aquaporins are likely important for osmoregulation and transepithelial water transport (Suzuki et al., 2007;Madsen,2012). Like mammals, birds concentrate urine in adaptation to terrestrial environments. Consequently, aquaporins are expressed in avian kidneys (Nishimura and Yang, 2013). P Water channels have also been localised in the brain, the gastroin- testinal tract and other organs of chicken, consistent with a role X for avian water channels in the regulation of fluid homeostasis and neuronal excitability (Yoshimura et al., 2011). There are 13 known mammalian aquaporins. In humans, aquaporins are involved in a wide range of physiological functions (Agre, 2004; Verkman, 2012). For instance, aquaporins play a role in urine concentration; they facilitate fluid secretion and skin hydration; they also play a role in the water balance of the cen- Figure 3 Confocal laser scanning micrograph showing the localisation of tral nervous system and in neuroexcitatory processes. In the eye, PIP2 proteins in a balsam poplar (Populus balsamifera) leaf midvein. The aquaporins are involved in lens transparency, intraocular pressure image was colour coded with an intensity look-up table (displayed in the regulation and visual signal transduction (Verkman, 2012). In upper right corner) in which black was used to encode background, and addition, malfunction of mammalian aquaporins has been impli- blue, green, yellow and red to represent increasing signal intensities. Strong cated in diverse deficiencies and diseases. PIP2 signals were observed in the plasma membrane of phloem cells (P), developing xylem cells (X) and in phloem ﬁbres (F). Arrows point to labelling in phloem and living/developing xylem cells. Controls with no primary Plant aquaporins antibody indicated minimal labelling (not shown); methods as described previously (Laur and Hacke, 2014a). Immunolabelling and imaging was Plant aquaporins represent a large protein family. More than 30 conducted by Ryan Stanﬁeld (University of Alberta). homologues have been identified in model plants like Arabidop- sis, poplar, grapevine, rice, maize and spruce (Maurel et al., with other isoforms; they may also facilitate CO2 diffusion across 2008; Gomes et al., 2009; Laur and Hacke, 2014a). Based on plasma and chloroplast membranes (Kaldenhoff, 2012). As pho- sequence homology, plant aquaporins are divided into subgroups. tosynthetic capacity is limited by the availability of CO2 in the Among those are the plasma membrane intrinsic proteins (PIPs), chloroplasts, this is an intriguing hypothesis; however, it remains the largest subfamily with 13 members in Arabidopsis. controversial (Chaumont and Tyerman, 2014). PIP2s are typically Why do plants have so many aquaporin genes? The answer to present in the plasma membrane of phloem cells (Figure 3). This this question may involve the fact that plants move very large has been found in poplar and in spruce (Laur and Hacke, 2014a, amounts of water from the soil into the atmosphere. Acquiring b). PIPs also seem to be involved in the recovery from xylem and transporting water is essential for terrestrial plants; the pro- embolism (Secchi and Zwieniecki, 2010). ductivity of agricultural crops and forest trees is often limited by Embolism repair likely involves the exchange of water the ability to uptake and transport water. See also: Plant–Water between xylem and phloem via living cells. Aquaporins have Relations been localised in these cells (Figure 4, arrows), suggesting At the whole-plant level, aquaporin (particularly PIP) regula- that water channels contribute to the radial movement of water tion facilitates rapid hydraulic adjustments to changes in light between xylem and phloem. Strong expression of aquaporins level, water availability and other external or internal factors. occurred in contact cells, that is, parenchyma cells with exten- ‘Gatekeeper’ cells seem to play a key role in these responses. sive pit contact to adjacent xylem vessels (Almeida-Rodriguez Gatekeeper cells are located in cell layers like the endodermis and Hacke, 2012). This suggests that water channels facili- in roots and the bundle sheath of leaves, and are thought to have tate the exchange of water between vessels and rays (Hacke, large impacts on whole-plant water relations (Shatil-Cohen et al., 2015). Strong expression is also seen in the vascular cambium 2011; Laur and Hacke, 2013, 2014a; Chaumont and Tyerman, (Figure 4) and in other meristems (Almeida-Rodriguez and 2014). Hacke, 2012; Péret et al., 2012; Plavcová et al., 2013). PIPs are further divided into PIP1 and PIP2 subgroups (Kam- merloher et al., 1994). Both subgroups are generally localised in tissues characterised by large fluxes of water such as vascu- Future Directions lar tissue, suggesting important roles in supporting long-distance transport in the xylem and/or phloem. PIP1s are not very efficient Since AQP1 was discovered in erythrocytes, hundreds of aqua- as water channels but are activated when assembled in tetramers porin homologues have been identified in all kingdoms of life.

Acknowledgements

We thank Ryan Stanfield for providing the image shown in R Figure 3. C

P X References

Agre P, Preston GM, Smith BL, et al. (1993) Aquaporin CHIP: the archetypal molecular water channel. American Journal of R Pi Physiology-Renal Physiology 265: F463–F476. Agre P (2004) Aquaporin water channels (Nobel Lecture). Ange- wandte Chemie International Edition 43: 4278–4290. Almeida-Rodriguez AM and Hacke UG (2012) Cellular localization of aquaporin mRNA in hybrid poplar stems. American Journal of Botany 99: 1249–1254. Beitz E, Wu B, Holm LM, Schultz JE and Zeuthen T (2006) Point mutations in the aromatic/arginine region in aquaporin 1 allow passage of urea, glycerol, ammonia, and protons. Proceedings of the National Academy of Sciences of the United States of America Figure 4 In situ mRNA hybridisation of the aquaporin gene PgPIP1;2 in a young stem of white spruce (Picea glauca). Regions of aquaporin expression 103: 269–274. are indicated by dark purple staining. Strong labelling was found in xylem (X) Boursiac Y, Boudet J, Postaire O, et al. (2008) Stimulus-induced rays (arrows), cambium cells (C), phloem (P) and resin ducts (R). Pi = pith. downregulation of root water transport involves reactive oxygen Rays allow water to move radially between xylem and phloem. Negative species-activated cell signalling and plasma membrane intrinsic controls hybridised with sense probes showed no/minimal labelling (not protein internalization. The Plant Journal 56: 207–218. shown). Methods as described previously (Laur and Hacke, 2014a). Carbrey JM, Gorelick-Feldman DA, Kozono D, et al. (2003) Aquaglyceroporin AQP9: solute permeation and metabolic control of expression in liver. Proceedings of the National Academy The principal function of aquaporins is to increase water flow of Sciences 100: 2945–2950. rates across membranes. This is a fundamental biological func- Carbrey JM and Agre P (2009) Discovery of the aquaporins and tion that impacts many complex processes such as kidney func- development of the field. In: Aquaporins, pp. 3–28. Berlin: tion and skin hydration in humans and water uptake by plant Springer. roots. In future years, many exciting case studies may shed light Chaumont F and Tyerman SD (2014) Aquaporins: highly regulated on specific functions of aquaporins in diverse organisms. This channels controlling plant water relations. Plant Physiology 164: will eventually provide us with a more complete answer to the 1600–1618. question of ‘what aquaporins are for’. Danielson JÅ and Johanson U (2010) Phylogeny of major intrinsic Many intriguing questions are unresolved. Beginning with proteins. In: MIPs and Their Role in the Exchange of Metalloids, human aquaporins, it may be possible to develop aquaporin mod- pp. 19–31. Berlin: Springer. ulators for therapy of glaucoma and other diseases. In the field Deen P, Verdijk M, Knoers N, et al. (1994) Requirement of human of plant science, one may ask why there are so many plant aqua- renal water channel aquaporin-2 for vasopressin-dependent con- porins. Are there key aquaporins in specific tissues/organs and centration of urine. Science 264: 92–95. for specific physiological roles? If so, which ones are particularly Eriksson UK, Fischer G, Friemann R, et al. (2013) Subangstrom resolution X-ray structure details aquaporin-water interactions. important? One could initially study this question in model plants Science 340: 1346–1349. and use this information for plant biotechnology applications. Farimani AB, Aluru N and Tajkhorshid E (2014) Thermodynamic This review highlights the role of aquaporins in facilitating insight into spontaneous hydration and rapid water permeation in water transport. However, we may also explore the functional aquaporins. Applied Physics Letters 105: 083702. roles of aquaporins in the transport of neutral solutes and gas. Gomes D, Agasse A, Thiébaud P, et al. (2009) Aquaporins are multi- Plant scientists are currently studying the influence of PIP1 aqua- functional water and solute transporters highly divergent in living porins on membrane permeability to CO2. Furthermore, recent organisms. Biochimica et Biophysica Acta (BBA) - Biomembranes immunolabelling experiments suggest that aquaporins are impor- 1788: 1213–1228. tant for phloem loading (R. Stanfield, U.G. Hacke, J. Laur, unpub- GuoL,WangZY,LinH,et al. (2006) Expression and functional lished manuscript); future work will likely improve our under- analysis of the rice plasma-membrane intrinsic protein gene fam- standing of the role of aquaporins in facilitating water exchange ily. Cell Research 16: 277–286. between xylem, phloem and nonvascular tissues. On an applied Hacke UG (2015) The hydraulic architecture of Populus. In: Hacke level, the efficiency and selectivity of aquaporins may inspire the UG (ed) Functional and Ecological Xylem Anatomy, pp. 103–131. development of biomimetic membranes. Such improved mem- Berlin, Heidelberg, New York: Springer. branes could perhaps be used for the desalination of seawater and Hedfalk K, Törnroth-Horsefield S, Nyblom M, et al. (2006) Aqua- brackish water. porin gating. Current Opinion in Structural Biology 16: 447–456.

Hill AE, Shachar-Hill B and Shachar-Hill Y (2004) What are aqua- Secchi F and Zwieniecki MA (2010) Patterns of PIP gene expression porins for? Journal of Membrane Biology 197: 1–32. in Populus trichocarpa during recovery from xylem embolism sug- Ishikawa Y, Skowronski MT, Inoue N and Ishida H (1999) 𝛼 gest a major role for the PIP1 aquaporin subfamily as moderators 1-Adrenoceptor-induced trafficking of aquaporin-5 to the apical of refilling process. Plant, Cell & Environment 33: 1285–1297. plasma membrane of rat parotid cells. Biochemical and Biophysi- Shatil-Cohen A, Attia Z and Moshelion M (2011) Bundle-sheath cal Research Communications 265: 94–100. cell regulation of xylem-mesophyll water transport via aquaporins

Kaldenhoff R (2012) Mechanisms underlying CO2 diffusion in under drought stress: a target of xylem-borne ABA? Plant Journal leaves. Current Opinion in Plant Biology 15: 276–281. 67: 72–80. Kammerloher W, Fischer U, Piechottka GP and Schäffner AR (1994) Shiels A and Bassnett S (1996) Mutations in the founder of the MIP Water channels in the plant plasma membrane cloned by immunos- gene family underlie cataract development in the mouse. Nature election from a mammalian expression system. Plant Journal 6: Genetics 12: 212–215. 187–199. Smith BL and Agre P (1991) Erythrocyte Mr 28,000 transmembrane Kozono D, Yasui M, King LS and Agre P (2002) Aquaporin protein exists as a multisubunit oligomer similar to channel pro- water channels: atomic structure molecular dynamics meet clinical teins. Journal of Biological Chemistry 266: 6407–6415. medicine. The Journal of Clinical Investigation 109: 1395–1399. Stein W and Danielli J (1956) Structure and function in red cell Laur J and Hacke UG (2013) Transpirational demand affects aqua- permeability. Discussions of the Faraday Society 21: 238–251. porin expression in poplar roots. Journal of Experimental Botany Suzuki M, Hasegawa T, Ogushi Y and Tanaka S (2007) Amphibian 64: 2283–2293. aquaporins and adaptation to terrestrial environments: a review. Laur J and Hacke UG (2014a) Exploring Picea glauca aquaporins Comparative Biochemistry and Physiology Part A: Molecular & in the context of needle water uptake and xylem refilling. New Integrative Physiology 148: 72–81. Phytologist 203: 388–400. Tanghe A, Van Dijck P, Dumortier F, et al. (2002) Aquaporin expres- Laur J and Hacke UG (2014b) The role of water channel proteins sion correlates with freeze tolerance in baker’s yeast, and over- in facilitating recovery of leaf hydraulic conductance from water expression improves freeze tolerance in industrial strains. Applied stress in Populus trichocarpa. Plos One 9: e111751. and Environmental Microbiology 68: 5981–5989. Luu DT, Martiniere A, Sorieul M, Runions J and Maurel C (2012) Tanghe A, Van Dijck P and Thevelein JM (2006) Why do microor- Fluorescence recovery after photobleaching reveals high cycling ganisms have aquaporins? Trends in Microbiology 14: 78–85. dynamics of plasma membrane aquaporins in Arabidopsis roots Tomkowiak E and Pienkowska JR (2010) The current knowledge of under salt stress. The Plant Journal 69: 894–905. invertebrate aquaporin water channels with particular emphasis on Macey RL and Farmer RE (1970) Inhibition of water and solute insect AQPs. Advances in Cell Biology 2: 91–104. permeability in human red cells. Biochimica et Biophysica Acta Törnroth-Horsefield S, Wang Y, Hedfalk K, et al. (2006) Structural (BBA)-Biomembranes 211: 104–106. mechanism of plant aquaporin gating. Nature 439: 688–694. Macey R (1984) Transport of water and urea in red blood cells. Amer- Tsujimoto H, Liu K, Linser PJ, Agre P and Rasgon JL (2013) ican Journal of Physiology-Cell Physiology 246: C195–C203. Organ-specific splice variants of aquaporin water channel AgAQP1 Madsen SS (2012) Aquaporins in fishes-expression, localiza- in the malaria vector Anopheles gambiae. Plos One 8: e75888. tion and functional dynamics. Front. Physio. 3: 434. DOI: Vera-Estrella R, Barkla BJ, Bohnert HJ and Pantoja O (2004) Novel 10.3389/fphys.2012.00434. regulation of aquaporins during osmotic stress. Plant Physiology Martre P, Morillon R, Barrieu F, et al. (2002) Plasma membrane 135: 2318–2329. aquaporins play a significant role during recovery from water Verkman A (2012) Aquaporins in clinical medicine. Annual Review deficit. Plant Physiology 130: 2101–2110. of Medicine 63: 303–316. Maurel C, Verdoucq L, Luu DT and Santoni V (2008) Plant aquapor- Wade JB, Stetson DL and Lewis SA (1981) ADH action: evidence for ins: membrane channels with multiple integrated functions. Annual a membrane shuttle mechanism. Annals of the New York Academy Review of Plant Biology 59: 595–624. of Sciences 372: 106–117. Nedvetsky PI, Tamma G, Beulshausen S, et al. (2009) Regulation Yoshimura K, Sugiura K, Ohmori Y, Aste N and Saito N (2011) of aquaporin-2 trafficking. In: Aquaporins, pp. 133–157. Berlin: Immunolocalization of aquaporin-4 in the brain, kidney, skeletal Springer. muscle, and gastro-intestinal tract of chicken. Cell and Tissue Nishimura H and Yang Y (2013) Aquaporins in avian kidneys: func- Research 344: 51–61. tion and perspectives. American Journal of Physiology-Regulatory, ZhangJ,LiD,ZouD,et al. (2013) A cotton gene encoding a plasma Integrative and Comparative Physiology 305: R1201–R1214. membrane aquaporin is involved in seedling development and in Péret B, Li G, Zhao J, et al. (2012) Auxin regulates aquaporin response to drought stress. Acta Biochimica et Biophysica Sinica function to facilitate lateral root emergence. Nature Cell Biology 45: 104–114. 14: 991–998. Pettersson N, Filipsson C, Becit E, Brive L and Hohmann S (2005) Aquaporins in yeasts and filamentous fungi. Biology of the Cell 97: Further Reading 487–500. Plavcová L, Hacke UG, Almeida-Rodriguez AM, Li E and Douglas Beitz E (ed). ISBN: 978-3-540-79884-2 (Print) 978-3-540-79885-9 CJ (2013) Gene expression patterns underlying changes in xylem (Online) (2009) Aquaporins. Handbook of Experimental Pharma- structure and function in response to increased nitrogen availability cology Volume 190. Springer. in hybrid poplar. Plant, Cell & Environment 36: 186–199.