Aquaporin
Synonyms
Historical Background
Water transport across cell membranes is an essential requirement for the biochemistry of life, yet it took more than two centuries of observations and research before transmembrane water channels termed aquaporins were discovered. For much of this time, it was assumed that water transport occurred either via simple diffusion or in certain instances was powered by active processes. As early as the eighteenth century, it was noted that adult frogs and toads absorb water across their ventral skin when dehydrated and placed in water. A century and a quarter later, it was discovered that the increased absorption of water across the skin could be enhanced by the injection of neurohypophysial extract (pituitrin), which was known to have antidiuretic effects in mammals. These observations were subsequently termed the water-balancing effect or Brunn reaction (Heller 1945) and paved the way for mechanistic studies of water transport in frog skin. Indeed, it was by comparing the diffusion in isolated frog skin to the in vivo osmotic water uptake of the intact animal that the first experimental evidence for facilitated water transport emerged in the laboratory of August Krogh (Hevesy et al. 1935). Using heavy water (D2O), it was noted that the abdominal and thigh skin of the edible frog (Rana esculenta) was bidirectionally much more permeable to D2O than skin isolated from other areas, and that the in vivo osmotic uptake of ordinary water (H20) was three- to fivefold higher than that expected from diffusion and the osmotic gradient between the blood and external water (Hevesy et al. 1935).
Subsequent experiments revealed that the Brunn reaction could be elicited in the isolated ventral skin of anurans, but in contrast to the notion that water must be actively transported in the distal renal tubules of Mammalia to promote antidiuresis, the experiments on frog skin implied that the increased water flux associated with the Brunn reaction is a passive process involving an increase in the permeability of the skin. By incorporating the Brunn reaction in a repeat of Hevesy, Hofer and Krogh’s (1935) experiments and analyzing the results with what became known as the flux-ratio theorem, Koefoed-Johnson and Ussing (1953) confirmed the earlier results and proposed that “the response to neurohypophysial extract of the water flow through the anuran skin may consist in an opening up of pores or creation of new pores to allow a more ready flow of solution” (1953). This was the first suggestion that water pores or channels should mediate the passive transport of water through biological membranes. Physiological studies of mammalian red blood cells further supported the existence of “water-filled pores in the membrane” (Paganelli and Solomon 1957), which could be reversibly closed in the presence of mercurials or excess cysteine that bind buried sulfhydryl groups in the pores (Macey and Farmer 1970). These latter studies lead the authors to observe “that water channels transport water and very little else” (Macey and Farmer 1970). Although the first visual evidence of such elusive pores was attained through electron microscopic observations of protein aggregates appearing in the urinary bladder membranes of toads in response to vasopressin, it was the isolation of proteins from the membranes of human red blood cells that eventually led to the discovery and proof of aquaporins.
With hindsight it is now known that the very first aquaporin to be sequenced and structurally analyzed was isolated from rat and calf lenses and termed the major intrinsic polypeptide (MIP) of lens membrane; however, although the predicted structure of this protein was consistent with an aqueous channel with six membrane-spanning domains and intracellular amino- and carboxy-termini, its primary function was considered as a gap junction protein (Gorin et al. 1984). Parallel studies conducted on human erythrocytes, however, took advantage of earlier observations that mercurials were associated with closure of the putative pores. These latter studies succeeded in isolating proteins (band 3, 80–100 kDa and band 4.5, 35–60 kDa) that bound a mercury compound ([203Hg]-p-(ch1oromercuri)benzenesulfonate, PCMBS) and were correlated to the inhibition of water influx as measured by nuclear magnetic resonance (Benga et al. 1986). Although both bands had been associated with anion or glucose transport, respectively, it was suggested that “It remains possible that a minor membrane protein that binds PCMBS is involved in water transport” (Benga et al. 1986). By chance, a 28 kDa integral membrane protein was indeed isolated from human erythrocytes and renal tubules by other investigators (Denker et al. 1988) but was initially considered to be a breakdown product of Rh(D) blood group antigens. The 28 kDa peptide nevertheless turned out to represent a nonglysoylated form of the 35–60 kDa higher molecular weight (HMW 28 kDa)-protein (Denker et al. 1988) and was termed channel-like integral membrane protein of 28 kDa (CHIP28) following initial peptide sequencing and isolation of the cDNA. The structural features of the deduced protein closely resembled that of bovine MIP, and subsequent heterologous expression in frog oocytes followed by hyposmotic shock demonstrated for the first time the water transporting property of the channel (Preston et al. 1992). Evolutionary studies had already established that MIP-related proteins are found in bacteria (GlpF), plants (TIP, NOD26), insects (Bib), and mammals (MIP) (Pao et al. 1991), and the name “aquaporins” was proposed to encompass the protein family (Agre et al. 1993). CHIP28, which represented the first functionally defined water channel, was renamed AQP1, and MIP, which is also a water channel but which also harbors cell-to-cell adhesive properties, was renamed AQP0. Ten years later, and more than two centuries after the observations of water uptake in frogs, the Nobel Prize for Chemistry was awarded to Peter Agre for his work in the discovery of aquaporins. Since then, the field has expanded exponentially with >100,000 related nucleotides now sequenced from all domains of life.
Structure
Aquaporin crystallographic data in Prokaryota and Eukaryota
Group | PDB | Ortholog | Resolution (Å) | Organism |
---|---|---|---|---|
Archaea | 2F2B, 2EVU | AqpM | 1.68–2.30 | Methanothermobacter marburgensis |
3NE2 | AqpM | 3.00 | Archaeoglobus fulgidus | |
Bacteria | 1FX8 | GlpF | 2.20 | Escherichia coli |
1LDA, 1LDF, 1LDI | GlpF | 2.10–2.80 | Escherichia coli | |
1RC2 | AqpZ | 2.50 | Escherichia coli | |
2ABM | AqpZ | 3.20 | Escherichia coli | |
2O9D-G | AqpZ | 1.90 | Escherichia coli | |
3NKA, 3NKC, 3NK5 | AqpZ | 2.40–3.00 | Escherichia coli | |
Plantae | 2B5F, 1Z98 | PIP2;1 | 2.10–3.90 | Spinacia oleracea |
3CN5, 3CN6, 3CLL | PIP2;1 | 2.05–2.95 | Spinacia oleracea | |
4IA4 | PIP2;1 | 3.10 | Spinacia oleracea | |
4JC6 | PIP2;1 | 2.15 | Spinacia oleracea | |
5I32 | TIP2;1 | 1.18 | Arabidopsis thaliana | |
Plasmodium | 3CO2 | PfAqp | 2.05 | Plasmodium falciparum |
Fungi | 2W2E, 2W1P | Aqy1 | 1.15–1.40 | Pichia pastoris |
5BN2 | Aqy1 | 1.30 | Pichia pastoris | |
3ZOJ | Aqy1 | 0.88 | Saccharomyces cerevisiae | |
Mammalia | 1SOR | AQP0 | 3.00 | Ovis aries |
3M9I | AQP0 | 2.50 | Ovis aries | |
3 J41 | AQP0 | 25.00 | Ovis aries I Homo sapiens | |
1YMG | AQP0 | 2.24 | Bos taurus | |
2B6O, 2B6P | AQP0 | 2.40 | Bos taurus | |
2C32 | AQP0 | 7.01 | Bos taurus | |
1FQY | AQP1 | 3.80 | Homo sapiens | |
1IH5 | AQP1 | 3.70 | Homo sapiens | |
1H6I | AQP1 | 3.80 | Homo sapiens | |
4CSK | AQP1 | 3.28 | Homo sapiens | |
1J4N | AQP1 | 2.20 | Bos taurus | |
4NEF | AQP2 | 2.75 | Homo sapiens | |
2D57 | AQP4 | 3.20 | Rattus norvegicus | |
2ZZ9 | AQP4 | 2.80 | Rattus norvegicus | |
3D9S | AQP5 | 2.00 | Homo sapiens | |
5DYE, 5C5X | AQP5 | 2.60–3.50 | Homo sapiens |
Aquaporinstructure. General topology of aquaporins showing the six transmembrane α-helices (1, 2, 4–6, 8), the two Asn-Pro-Ala (NPA) motifs, the five loops (A–E), and intracellular amino- and carboxy-terminal domains. Molecules and domains associated with posttranslational modifications, gating, and trafficking are indicated
Aquaporin 3D structure. (a) Extracellular view of the quaternary structure of human AQP5 (3D9S) showing cartoon renderings of the four protomeric water channels (red, green, yellow, and blue) and the permeation paths of water (wheat spheres). (b) Monomeric lateral view of the water path (wheat spheres) through human AQP5 showing the aromatic-arginine (ar/R, spacefill spheres) and Asn-Pro-Ala (NPA, sticks) constrictions. (c) B-factor putty render of tetrameric sheep AQP0 (green, cyan, magenta, yellow) with interacting residues associated with cell-to-cell adhesion shown as spacefill (white). (d) Octomeric arrangement of double-layered AQP0 tetramers showing aligned interactions between residues in opposing membranes
Major solvents and solutes shown to permeate through archaeal, bacterial, protozoon, plant, fungal, nematode, arthropod, and vertebrate aquaporins. The aromatic arginine (ar/R) constriction residues are shown for each channel with positions P1 in transmembrane domain (TMD)-2, P2 in TMD5, and LE1and LE2 in loop E
Aquaporin grade | Ortholog | ar/R | Permeant | |||
---|---|---|---|---|---|---|
P1 | P2 | LE1 | LE2 | |||
Classical Aqp4-related aquaporins | AQP0 | F | H | A | R | Water, CO2 |
AQP1 | F | H | C | R | Water, CO2, NO, H2O2, NH3 | |
AQP2 | F | H | C | R | Water | |
AQP4 | F | H | A | R | Water, CO2 | |
AQP5 | F | H | C | R | Water, CO2 | |
AQP6 | F | H | C | R | Water, glycerol, urea, anions, NO3−, CO2, NH3 | |
Bib | S | C | ? | R | Cations | |
Drip | F | H | A | R | Water | |
Prip | F | H | A/S | R | Water, urea | |
Eglp | F | A/S | A/S/G | R | Water, glycerol, urea, polyols, trehalose | |
PIP | F | H | T | R | Water, CO2, H2O2 | |
Aqp8-related | AQP8 | H | I | A/G | R | Water, glycerol, urea, NH3, H2O2 |
Nematode Aqp8L | H | I | A | R | Water | |
Trematode Aqp8L | A | A | C | A/S | Water | |
TIP | H | I | A/G | R | Water, glycerol, urea, CO2, H2O2, NH3 | |
XIP | I/Q | A/I/T | A | R | Water, glycerol, urea, boric acid, H2O2 | |
HIP | H | H | A | R | Unknown | |
Aqy1, Aqy2 | F | H | A/T | R | Water | |
Unorthodox aquaporins | AQP11 | T/P | L | A | L | Water, glycerol |
Plant SIP | I/L/V | I/L/V | P | I/N | Water, metalloids, H2O2 | |
Aquaglyceroporins | AQP3 | F | G | Y | R | Water, glycerol, urea, antimonite, arsenite, polyols |
AQP7 | F | G | Y | R | Water, glycerol, urea, antimonite, arsenite, NH3 | |
AQP9 | F | A/S | C | R | Water, glycerol, urea, carbamides, polyols, purines, pyrimidines, antimonite, arsenite, CO2, NH3 | |
AQP10 | G | G/S | I/F/Y | R | Water, glycerol, urea; antimonite, arsenite | |
AQP13 | F | G | Y | R | Water, glycerol, urea | |
Arthropod Glp | F/Y | A/T/H | A/F/T | R | Water, glycerol, urea | |
Nematode Glp | W | G | Y | R | Water, glycerol | |
Plasmodium Glp | W | V | G | R | Water, glycerol, NH3 | |
Fps1 | W | G | F | R | Water, glycerol, methylamine, NH3, antimonite, arsenite, boric acid | |
NIP | A/G/W | A/I/S | A/G | R | Water, glycerol, formamide, arsenite, boric acid, silicic acid, NH3 | |
Bacteria | AqpZ | F | H | T | R | Water |
GlpF | W | G | F | R | Water, glycerol, urea, antimonite, arsenite, polyols, lactate | |
Archaea | AqpM | F | I/V/L | A/S | R | Water, glycerol |
Some aquaporins evolved the ability to form intercellular junctions, including vertebrate Aqp0, an N-terminal truncated M23 isoform of mammalian AQP4, and the Bib channel of Drosophila. While the molecular basis for the cell-to-cell adhesion of Bib remains to be determined, the structural interactions facilitating adhesion of Aqp0 and AQP4M23 channels are different. In mammalian AQP0, four proline residues (Pro38, Pro109, Pro110, Pro123) and an arginine (Arg113) in extracellular loops A and C form a triangle of residues on each protomer that interact with the same positions in the protomeric channels in the opposing membrane (Fig. 2c). The Pro38 residues on loop A form a unique rosette-like structure in the center of the octomeric junction, and the remaining residues hydrogen bond to maintain a precisely stacked double layered arrangement of the opposing tetramer (Fig. 2d). By contrast, AQP4M23 junctions are formed by Pro139 and Val142 at the extracellular end of transmembrane domain 3, which hydrogen bond to the same residues of only one of the protomers of four opposing tetramers. In this way, the junctions formed by an AQP4M23 tetramer in one membrane interact with four separate AQP4M23 tetramers in the juxtaposed membrane. Consequently, the channels are not stacked in register as for AQP0 but are arranged in a rotated lattice with each protomer partially obstructing the water path of the channel in the opposing membrane (see Wspalz et al. 2009; Fig. 4 for an illustration).
Evolution and Diversity
Aquaporin evolution and diversity. (a) Bayesian midpoint rooted codon tree of prokaryotic aquaporins together with plant NIPs, with posterior probabilities shown at each node. (b) Bayesian codon tree of eukaryotic aquaporins rooted with archaean AqpM, with posterior probabilities shown at each node. (c) Phylogenetic distribution of eukaryotic aquaporins arranged in four grades. N refers to the number of paralogs in the given organism
Until recently, it was thought that glycerol transporters of vascular plants, termed nodulin 26-like intrinsic proteins (NIPs), arose through horizontal gene transfer of AqpZ-type channels (Abascal et al. 2014). However, recent phylogenetic evidence suggests that bacterial AqpN-type channels were the likely origin of NIPs with the last common ancestor closely related to nitrite-oxidizing members of the Chloroflexi phylum (Fig. 3a) (Finn and Cerdà 2015).
Amongst eukaryotes, the gene copy number and diversity of channels varies considerably between the different taxonomic lineages but can be grouped into four grades of classical aquaporins related to Aqp4-type channels, Aqp8-type channels, unorthodox channels, and classical aquaglyceroporins (Fig. 3b, c). The high gene copy number in protozoan organisms is surprising, but indicates that there is no relationship between copy number and organism complexity, and may instead reflect the ability to adapt to changing environments. Evolution of the superfamily in the different taxonomic lineages is characterized by multiple gene duplications, either through whole genome duplications or local tandem duplications and subsequent differential gene loss (Abascal et al. 2014; Finn et al. 2014, 2015). One unusual case of aquaporin gene evolution has been established for insect glycerol transporters. In this instance, novel Prip-like channels, which are phylogenetically related to Aqp4 orthologs (Fig. 3b), duplicated and neofunctionalized in basal hexapods, whereby one of the ar/R residues (His on transmembrane domain 5) was replaced by smaller uncharged residues (mostly Ser and Ala). This critical alteration seems to have opened the pore to allow the passage of glycerol and other small uncharged solutes. The increased efficiency of glycerol transport and positive selection of these hexapod-specific channels, termed entomoglyceroporins (Eglps), is thought to have caused the loss of the classical aquaglyceroporins in holometabolous and hemipteran insects. By contrast, with the exception of green algae (Chlorophyta), land plants (Embryophyta), and some single-celled organisms, glycerol transport is achieved via the classical aquaglyceroporins (Glps) in all other taxa studied to date. The neofunctionalization and gene replacement due to increased efficiency of glycerol transport represents a form of Darwinian evolution at the molecular level and can thus be considered as molecular supplantation.
Amongst protists and multicellular organisms, the aquaporin gene family is most diverse in algae, plants, and vertebrates. These lineages retain high gene copy numbers associated with polyploidy with up to 71 paralogs in upland cotton and at least 42 paralogs in Atlantic salmon (Fig. 3c). In green algae, eight types of aquaporin have been identified including plasma membrane intrinsic proteins (PIPs), algal-specific forms (MIPA-E), GlpF-like intrinsic proteins (GIPs), and small basic intrinsic proteins (SIPs), while the embryophyte superfamily consists of seven major phylogenetic groups, which evolved by both horizontal and vertical gene transfer (Anderberg et al. 2011; Abascal et al. 2014). The NIPs and GIPs, which represent the major glycerol transporters in plants, have their origins in bacteria, while PIPs, X intrinsic proteins (XIPs), and SIPs likely evolved in unicellular eukaryotes and were vertically transferred to algae and plants. Conversely, tonoplast intrinsic proteins (TIPs) and hybrid intrinsic proteins (HIPs) appear to have their origins in ancient ancestors of Embryophyta, which probably retained all seven of the aquaporin groups as exemplified by mosses (Danielson and Johanson 2008). Three of these gene groups, however, were subsequently lost prior to and during the evolution of flowering plants (Angiosperms), with GIPs and HIPs disappearing prior to the evolution of paired leaf-seed plants (Dicotyledonae) and XIPs prior to the evolution of single leaf-seed plants (Monocotyledonae) (Danielson and Johanson 2008).
Each of the four grades of aquaporin outlined above has been found in basal metazoan organisms, including Porifera (sponges) and Cnidaria (jellyfish and corals), although Aqp4-like (Aqp4L) and Aqp8-like (Aqp8L) channels have yet to be identified in Porifera and Cnidaria, respectively (Fig. 3c). These data nevertheless suggest that the four grades may have been an ancient feature of eukaryotic organisms, with the lack of a particular grade indicating lineage-specific gene loss. Amongst Protostomia, such gene loss is exemplified by Aqp4L channels in Nematoda and Aqp8L channels in Arthropoda (Finn and Cerdà 2015). All four grades are nevertheless present in basal Deuterostomia, with 17 subfamilies (Aqp0–Aqp16) now identified in vertebrates (Finn et al. 2014). Modern placental mammals, however, have only retained 13 functional forms of these subfamilies (Aqp0–Aqp12), while monotremes still harbor the Aqp13 and -14 paralogs. Selective tandem evolution of Aqp2, -5, and -6 paralogs, which play vital roles in the water conservation of all extant tetrapods, occurred exclusively in the sarcopterygian (lobed finned) lineage and is considered to have been permissive for the adaptation of vertebrates to land (Finn et al. 2014).
Genomic structures and karyotypic distributions of eukaryotic aquaporins. Annotated genes are shown to scale and localized in the genomes of human (Homo sapiens), zebrafish (Danio rerio), fruit fly (Drosophila melanogaster), and thale cress (Arabidopsis thaliana) based upon Ensembl. Solid boxes represent exons with grey triangles indicating coding direction. Gene clusters are linked by dotted lines. Numbers above broken introns indicate length in kilobases (kb)
Permeability
The molecular transport properties of aquaporins are typically tested experimentally using homologous or heterologous expression experiments in amphibian oocytes, cultured cell lines, and yeast cells or from reconstituted aquaporins in liposomes. Such experiments have revealed that nearly all aquaporins transport water, while certain grades including the Aqp8-related channels and aquaglyceroporins are multifunctional (Table 2). A number of exceptions to water transport have nevertheless been documented, including loss of this function in laboratory strains of yeast Aqy2, some plant PIP1s and NIP6s, and Drosophila Bib, which evolved into a cation transporter (K+ > Na+). Mammalian AQP0 has an apparent low-intrinsic water permeability; however, this is likely a derived feature, since piscine-Aqp0 orthologs, including both genomic duplicates in zebrafish and all four paralogs in tetraploid Atlantic salmon, transport water efficiently (Chauvigné et al. 2015). In addition to water, most eukaryotic channels are also considered capable of permeating hydrogen peroxide (H2O2) to mediate cell signaling or alleviate oxidative stress generated by mitochondria or chloroplasts (Bienert and Chaumont 2014). A number of vertebrate and plant aquaporins have been shown to transport gases, such as NH3 and CO2, although the molecular mechanism is still debated.
The multifunctional passage of larger solutes, such as glycerol, is an inherent property of the classical aquaglyceroporins, which typically retain small uncharged residues in P2 of the ar/R selectivity filter, rather than the conserved His of the classical water channels. Indeed, mutation of the His to Ala or Ser in the Eglps of hexapods converted these Aqp4-related channels into efficient glycerol transporters. Ion transport is rare for the aquaporin superfamily but has nevertheless evolved independently in the Drosophila Bib and mammalian AQP6 channels.
Regulation
Beyond osmotic pressure associated with changing solute concentrations, cellular control of the rate of molecular permeation through aquaporin pores is achieved primarily via gating while the channel is integrated in the target membrane or by trafficking to and from the membrane. Gating has been observed for plant, fungal, and vertebrate aquaporins where the orthologous pores are closed or opened by mechanical stress, altered [H+] and [Ca2+], or phosphorylation/dephosphorylation of specific residues. In each case, the creation or removal of additional electrochemical barriers or conformational changes is thought to mediate the open or closed state (Törnroth-Horsefield et al. 2010). For example, during drought stress, dephosphorylation of two conserved Ser residues in plant PIPs causes pore closure by extension of a Leu residue on loop D into the cytoplasmic region of the channel, but during flooding, reduced intracellular pH associated with anoxia also closes the pore through protonation of a conserved loop D His residue. The loop D Leu closure mechanism may also be invoked by the binding of Ca2+ ions, which causes hydrogen bond interactions between loop D, loop B, and N-terminal residues. In fungal Aqy1, an N-terminal Tyr residue is thought to be responsible for gating the cytoplasmic region of the pore, which can be modulated either through mechanical stress or potentially through phosphorylation/dephosphorylation of a loop B Ser residue. Mechanical stress in the form of pressure pulses is further suspected to invoke gating of some plant aquaporins. Conversely, extracellular pH and intracellular [Ca2+] regulate the channel permeability of vertebrate AQP0, where the position of a single His residue at the extracellular junction of transmembrane 2 and loop A is critical for pH-regulated water permeability, which varies between fish and mammals, while elevated intracellular [Ca2+] acting through calmodulin closes the pore. Extracellular acidity further converts AQP3 from a water and glyerol transporter to predominantly a glycerol transporter between pH 6.1 and 6.4 but closes the pore at pH < 6.1, while phosphorylation/dephosphorylation of a loop B Ser residue is suggested to regulate water permeation through AQP4, although this latter control remains controversial. With the exception of the gating role of plant PIPs, however, the physiological significance of channel gating still remains to be established.
The predominant regulatory mechanism of vertebrate aquaporins is trafficking. During membrane protein trafficking, protein sorting signals are recognized by components of the trafficking machinery, directing them to their target locations. For aquaporins, sorting signals involve multiple posttranslational modifications of the N- or C-termini, or the internal loops, typically involving phosphorylation/dephosphorylation events of specific residues. In mammals, the trafficking of AQP2 in the kidney collecting duct has been extensively investigated and represents the canonical example of aquaporin trafficking. This involves the antidiuretic hormone vasopressin that, upon dehydration, triggers the redistribution of AQP2 from intracellular storage vesicles to the apical membrane. During this mechanism, protein kinase A phosphorylation of Ser256 is a prerequisite for targeting to the apical membrane, whereas ubiquitination of Lys270 triggers AQP2 internalization, after which it can be stored for another round of vasopressin-mediated trafficking, or targeted for degradation. A number of proteins have also been shown to bind AQP2 and regulate its trafficking, predominantly via the AQP2 C-terminal region. Examples include heat shock protein 70 (hsp70/hsc70) and LYST interaction protein 5 (LIP5), as well as Spa-1. Protein-protein interactions involving the C-terminus have also been demonstrated to regulate AQP0, AQP4, and AQP5 trafficking (Sjöhamn and Hedfalk 2014).
Physiological Functions
Aquaporin expression in humans. Expression patterns are annotated based upon the presence of mRNA or protein in a given tissue, with aquaporins colored according to their grade. Data are derived from the EMBL Expression Atlas, and literature sources cited in the text
Aquaporin expression in anuran amphibians. (a) During dehydration, neurohypophysial peptides, arginine vasotocin (AVT), and hydrins induce water uptake via aquaporins in the ventral patch and thigh skin and recycling of water via aquaporins in the urinary bladder and kidneys. The figure is modified after Suzuki et al. (2015). (b) AQP2 functions as the major channel recycling water in the kidneys, but different paralogs of AQP6 (ventral skin-type or urinary bladder-type) and AQP5 are recruited for water recycling depending upon the ecology of the species
Aquaporin expression in teleosts. Colored dots refer to the tissue distribution in adult zebrafish, while white dots represent data reported for other species. In some species, the anterior intestine is indicated by the stomach, while the brain includes chemosensory and mechanosensory organs. The figure is modified after Finn and Cerdà (2011)
Aquaporin expression in insects. Colored dots refer to the tissue distribution in adult Drosophila, while white dots represent data reported for other species of insect. Data are compiled from the Fly Atlas and literature sources cited in the text. The image is modified under the GNU Free Documentation License
Amongst protists, the single channel or suite of paralogous aquaporins are important for solute transport, cell volume regulation in response to hyposmotic stress, osmotaxis, glycerol flux associated with energy metabolism, encapsulation, germination, and expulsion of toxic metabolic byproducts. For fungal yeasts, aquaporins and aquaglyceroporins are considered important for freeze tolerance, water transport during development, osmosensing, modulation of cell surface properties for substrate adhesion and formation of cell biofilms. Within filamentous fungi, aquaglyceroporins are considered important for fruiting body formation and in the water flow and nutrient exchange of ectomycorrhizas.
Aquaporin expression in plants. (a) Transcript expression levels of 33 aquaporin paralogs in the root, leaf, fruit, and flower of Arabidopsis thaliana. Transcript levels are shown as fragments per kilobase of exon per million fragments mapped (FPKM). Data are derived from the EMBL Expression Atlas under the Creative Commons Attribution 4.0 International License, and literature sources cited in the text. (b) Water transport pathways in leaves and (c) roots. Aquaporins are recruited to the cell-to-cell pathway for transcellular water flow. Redrawn from Maurel et al. (2015) with permission from The American Physiological Society
Summary
Despite eluding scientists for centuries, aquaporins are now found in virtually every organism studied, often with surprisingly broad repertoires in both prokaryotes and eukaryotes. The core transmembrane domains are conserved in all channels to form a central pore that primarily facilitates the passage of water and other small uncharged solutes, while the extracellular and intracellular loops and terminal domains are the major sites for regulation. Control of water and solute flux is typically achieved via the osmotic pressure, or gating and trafficking associated with altered pH, divalent ions, and phosphorylation/dephosphorylation events. The channels can play important homeostatic roles within intracellular compartments or between the plasma membrane and extracellular space, while a combination of different paralogs located in the apical or basolateral membranes of multicellular organisms is typically responsible for transcellular fluid transport. Although advances have been made in our understanding of aquaporin biology, there remains a general lack of crystallographic models for most of the identified orthologs. To date, there are no crystals available for metazoan aquaglyceroporins, Aqp8-type channels, or unorthodox aquaporins. Such data are essential for the accurate assessment of the structural mechanisms underlying the differences in water and solute transport, as well as their inhibition and molecular regulation, and will be of paramount importance for drug discovery. In this respect, the development of specific blockers will be highly advantageous for biomedical research. Very little is known of the function of the unorthodox channels, despite their broad expression patterns in insects and vertebrates. Similarly, although evolutionary studies have opened a window on the great variety of channels in prokaryotic and eukaryotic organisms, the positive selection and apparent nonredundant functions of multiple closely related channels have yet to be elucidated. Based upon the established biological importance of aquaporins in animal health, cancer, crop biology, and infective or parasitic diseases, however, the water channel proteins of different organisms remain highly attractive as therapeutic targets.
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