Water Channels Secondary article

Landon S King, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Article Contents
Peter Agre, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA . Discovery of Aquaporin-1
. Transmembrane Structure
. Channel Properties
Water can cross plasma membranes by diffusion through the lipid bilayer or by channel-
. Physiological Regulation
mediated water movement. Aquaporins are transmembrane proteins that are selectively
. Summary
permeable to water. These proteins are the first identified molecular water channels.

Discovery of Aquaporin-1
Water can cross plasma membranes by two basic path-
ways: diffusion through the lipid bilayer or channel-
mediated water movement. The existence of water-specific
channels was strongly suggested by observations made
over several decades: (1) osmotically driven water move-
ment across red blood cell membranes and renal proximal
tubular epithelium was too rapid to be explained by
diffusion through the membrane; (2) mercurial compounds
could reversibly inhibit the high osmotic permeability
across red cell and proximal tubule membranes; and (3)
radiation inactivation studies of membrane water perme-
ability in red blood cells and renal proximal tubule
epithelial cells implicated a membrane protein of 30 +
3 kDa as the mediator of high water permeability in those
tissues. Multiple candidate proteins have been proposed as
the molecular water channel, including the band 3 anion
exchanger, the sodium-independent glucose transporter
GLUT1, and CFTR, but none satisfied the physiologically
defined characteristics (reviewed in King and Agre, 1996).
Aquaporin-1 (AQP1), the archetypal water channel
protein, was serendipitously identified during studies of the
human red cell Rh protein. A 28 kDa protein thought to be
a proteolytic fragment of the Rh polypeptide proved to be a
discrete integral membrane protein, abundant in red cells
and renal proximal tubules. Partial sequencing of the
amino terminus suggested homology with the major
intrinsic protein of lens (MIP); homology was confirmed
by cloning of the full-length cDNA from a human bone
marrow library. Kyte and Doolittle hydropathy analysis
predicted six bilayer spanning domains, which led to the
initial name CHIP28, for ‘channel-forming integral protein
of 28 kDa’. Several clues suggested that this newly
discovered membrane protein could be the long-sought
water channel. The number of copies of AQP1 protein in
red cells,  2  105 per cell, was similar to the predicted
number of water channels in red cells; radiation inactiva-
tion studies of native water channels predicted a protein
similar in size to AQP1; and the distribution in red cells and
renal proximal tubules was the same as that of the
physiologically defined water channel. Subsequent to its
demonstration as the first water channel (see Channel
Properties, below), CHIP28 was designated Aquaporin-1
(abbreviated AQP1) by the Human Genome Committee
(reviewed in King and Agre, 1996).
Transmembrane Structure
Hydrophobicity analysis of AQP1 suggested six bilayer
spanning domains. Antibody labelling of the amino and
carboxy termini of AQP1 demonstrated both to be
intracellular, leading to a proposed topology of three
extracellular loops (A, C and E) and two intracellular loops
(B and D; Figure 1). Vectorial proteolysis of functional
AQP1 molecules using the E1 epitope of avian coronavirus
confirmed the extracellular position of loops C and E, and
the intracellular location of loops B and D. The N-
glycosylation site for AQP1 is in loop A, proving its
extracellular location, while AQP2, 3, 4, and 5 have an N-
glycosylation consensus in loop C, further suggesting the
extracellular location of that region (reviewed in King and
Agre, 1996).
Each of the known aquaporins, as well as other members
of the MIP family, have a conserved Asn-Pro-Ala (NPA)
motif present in both the amino and carboxy terminal
halves of the molecule (Figure 1). Additionally, amino acids
flanking the NPA sequences are highly homologous
between family members. Recognition of this homology
has formed the basis for cloning strategies and identifica-
tion of new homologues. Like MIP, AQP1 was noted to
have internal homology between the first and second halves
of the molecule, with the greatest degree of homology
between the NPA motifs. Interestingly, loop B and loop E
are oriented at 1808 to each other on opposite sides of the
membrane, a unique biological orientation (Figure 1).
Within the MIP family, the amino terminal half of each
protein is more closely related to the amino terminal half of
other family members than are the carboxy terminal
halves. This observation led to the proposal that the amino
terminal half of the molecule subserves functions common
to all family members, while the carboxy terminal half
provides functional specificity.
Site-directed mutagenesis of residues surrounding the
two NPA motifs led to the prediction of an ‘hourglass’
model for the topology of AQP1, with loops B and E

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 Water Channels

Glycosylation sites
N
Loop A – AQP1 A C E
Loop C – AQP2, 3, 4, 5 Out
C E P C
N A
Hg inhibition site Membrane
A C
Loop E – AQP1, 2, 5 N A
P
N
N In
Out C
N A B D
Membrane P P
N A
H2 N
In
S S

D
NH2 B
PKA motifs
HOOC
S Loop B – AQP4
Loop D – AQP5 (a)
S
COOH – AQP2

C
COOH A
Repeat-1 Repeat-2 E
C Out
Figure 1 The topology of aquaporin-1. Shown schematically are the six P
N A
bilayer-spanning domains, with intracellular amino and carboxy termini. A N
P
Three extracellular loops (A, C and E) and two intracellular loops (B and D)
In
are formed; loops B and E fold into the lipid bilayer. The NPA motif is present
in both the amino and carboxy terminal halves of the molecule. The front B D
half (repeat-1) and back half (repeat-2) of the molecule are highly similar,
but are oriented on opposite sides of the membrane. Also shown are the
H2 N
sites for glycosylation, mercury inhibition and PKA phosphorylation
(proposed) for AQP1 or other aquaporins.

folding into the lipid bilayer to form the aqueous pore
(Figure 2; reviewed in King and Agre, 1996). Using highly
purified red cell AQP1 for reconstitution, electron diffrac-
tion of cryopreserved membrane crystals at tilts of up to
608 has provided 3–6 Å resolution of the AQP1 monomer
(Walz et al., 1997). These studies confirm the presence of six
bilayer-spanning a helices, and reveal an intrasubunit
structure consistent with the hourglass model. Atomic
resolution of the aqueous pore has yet to be achieved.
AQP1 assembles in the membrane as a homotetramer, as
demonstrated by hydrodynamic studies, freeze fracture of
proteoliposomes and renal proximal tubule cells, and
electron microscopic analyses of two-dimensional crystals
from purified functional AQP1 protein. The requirement
for tetrameric assembly is as yet unexplained, though may
reflect instability of the asymmetric monomer in the lipid
bilayer. Complementation studies by Jung and colleagues
using dimeric AQP1 mutants with and without mercury-
sensitive sites suggest that the tetramer comprises four
independent functional units (reviewed in King and Agre,
1996).
Protein immunoblots of red cell membranes with
affinity-purified anti-AQP1 antibodies demonstrated a
discrete electrophoretic band of 28 kDa, the AQP1 core
protein, and a more diffuse electrophoretic band from 40 to
60 kDa, the core protein plus an Asn-linked complex
carbohydrate (Smith and Agre, 1991). The appearance and
HOOC
Figure 2 The hourglass model of aquaporin-1. A linear representation of
(b) six bilayer-spanning domains is shown in (a), with loops B and E folded
the
into the membrane. The amino and carboxy termini fold together to
generate the functional monomer; the aqueous pore is formed by the two
NPA motifs (b).
abundance of the upper band varies in different tissues.
Biochemical analysis of highly purified AQP1 revealed
glycosylation of only one of the four subunits forming the
functional tetramer. Elimination of the N-glycosylation
site in AQP1 did not alter its trafficking or function in the
Xenopus laevis expression system, although the role of
glycosylation in mammalian cells is most likely related to
membrane trafficking.
Channel Properties
Expression of AQP1 cRNA in X. laevis oocytes provided
the evidence that indeed AQP1 was a water-specific
channel (Preston et al., 1992). Osmotic water permeability
(Pf) reflects membrane water permeability under condi-
tions of an osmotic gradient across the membrane. Xenopus
laevis oocytes normally have very low water permeability,
but transfer of AQP1-injected oocytes to hypotonic

2 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net


solution led to swelling and rupture, with little change in
control-injected oocytes. The Pf of AQP1-injected oocytes
(200  10 2 4 cm s 2 1) was 8-fold greater than that of
control oocytes at 228C, and 30-fold greater at 108C. The
calculated Arrhenius activation energy (Ea) for the AQP1-
injected oocytes was 5 21 kJ mol 2 1, consistent with
channel-mediated water movement, whereas the Ea for
control oocytes was 4 42 kJ mol 2 1. The Pf and Ea values
for AQP1-injected oocytes were similar to those demon-
strated for physiologically defined water channels in red
cell membranes.
AQP1-mediated water movement is inhibited by HgCl2,
as had been shown for both red cells and renal proximal
tubule. Cysteine-scanning mutagenesis with systematic
substitution of serine for each of the four cysteines of
AQP1 revealed Cys189 to be the mercury-sensitive site in
the molecule (Figure 1; reviewed in King and Agre, 1996).
Insertion of larger amino acids into position 189 greatly
reduced osmotic water movement, raising the possibility
that Cys189 might be located near the aqueous pore.
However, protein immunoblots of Cys189 mutants with
diminished water permeability revealed incompletely
formed glycans, suggesting altered protein folding or
trafficking as an alternative cause of decreased water
permeability. Position 73 in loop B is analogous to Cys189
but located on the cytoplasmic face of the membrane.
Introduction of a cysteine into position 73 returned
mercury sensitivity to AQP1 mutants that had been
rendered mercury-insensitive by substitution for Cys189;
substitution of larger residues into position 73 again
reduced osmotic water permeability. These results sug-
gested that both position 189 and position 73 of AQP1 were
near the presumed mouth of the water channel, and led to
the proposal of the ‘hourglass’ model of AQP1 (Figure 2).
Patch clamp studies revealed no new ionic currents in
AQP1-injected oocytes until the point of rupture, provid-
ing evidence that the channel was water-specific. Recon-
stitution of purified AQP1 into proteoliposomes proved
that AQP1 does not require accessory proteins to exhibit
full function as a water channel, and further confirmed the
specificity for water, as urea, protons, hydroxyl ions,
ammonium ions, and salts were not transported. Claims of
AQP1-mediated ion transport have not been substan-
tiated. The unit water permeability of AQP1 in recon-
stituted liposomes was calculated (  3  109 H2O
molecules per subunit per second) and, when extrapolated
to the intact red cell, indicated that AQP1-mediated water
permeability was sufficient to explain the known water
permeability of the red cell. Recent studies using X. laevis
oocytes suggested CO2 permeation of AQP1 (reviewed in
Agre et al., 1998). As with ongoing investigations of the
permeability of aquaporins to other gases, interpretation
of physiological relevance of CO2 permeability is con-
founded by high background permeability, and the
implications of these observations remain to be under-
stood.
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Water Channels
While the earliest discovered aquaporins are truly water-
specific (AQP1, AQP2, AQP4, AQP5), several homologues
have now been identified that are permeable not only to
water but also to glycerol and other small solutes (AQP3,
rAQP7, hAQP7L, AQP9) (reviewed in Agre et al., 1998).
Phylogenetically, this may reflect the transition from
bacteria, which contain two MIP family members: one is
a true aquaporin (aqpZ in E. coli), and one functions as a
glycerol transporter (glpF in E. coli) (reviewed in Agre
et al., 1998). The structural differences that dictate channel
specificity are not yet known. Likewise, the physiological
significance of glycerol transport has yet to be identified.
Physiological Regulation
Ten mammalian aquaporins have been identified, each
with a distinct tissue distribution. Water transport
requirements at each of these sites are likewise quite
distinct. It is easy to imagine that multiple regulatory
mechanisms will be identified to explain the specificity of
distribution, timing and abundance of expression, and
control of function of each aquaporin. With the exception
of AQP2, these mechanisms are poorly understood.
Aquaporin expression and regulation in several organs is
described below, with speculation about the physiological
role that each might play.
Kidney
Of the 180 litres of glomerular filtrate formed each day, 80–
90% is reabsorbed in the proximal tubule and descending
thin limb of the Henle loop, segments known to have
constitutively high water permeability. The ascending thin
and thick limbs of the Henle loop, distal convoluted tubule
and connecting tubule are known to be largely imperme-
able to water. The remaining 10–20% of the glomerular
filtrate is reabsorbed in a vasopressin-dependent fashion in
the collecting duct. Water permeability of the individual
nephron segments correlates closely with water channel
expression at those sites (reviewed in Knepper et al., 1996).
AQP1 is abundantly expressed throughout the proximal
tubule and descending thin limb; it constitutes approxi-
mately 4% of proximal tubule brush border protein. AQP1
is present in reduced amount on the basolateral membrane,
and there is no intracellular pool. AQP1 density and unit
water conductance are sufficient to account for the known
water permeability of the proximal tubule and descending
thin limb. The vascular supply of the renal medulla, the
vasa recta, is critical to generation and maintenance of an
axial osmotic gradient through the medulla. Nielsen and
colleagues recently demonstrated both mercury-inhibita-
ble water permeability and presence of AQP1 in the apical
and basolateral membrane of endothelial cells of the
descending vasa recta, thereby providing anatomical and
3
 Water Channels
functional evidence that AQP1 mediates vasa recta water
transport.
AQP2 is located in the principal cells of the collecting
duct. Under resting conditions, AQP2 is found primarily in
intracellular vesicles beneath the apical membrane; lesser
amounts are present at the basolateral membrane. In
response to arginine vasopressin (AVP) binding of the V2
receptor at the basolateral membrane, the C-terminus of
AQP2 is phosphorylated, and vesicle targeting proteins
including VAMP-2 facilitate translocation of the AQP2-
containing vesicles to the apical membrane (reviewed in
Knepper et al., 1996). AQP2 redistribution to the apical
membrane has been closely correlated with a dramatic
increase in membrane water permeability. The link
between AQP2 and AVP was strengthened by studies
demonstrating that Brattleboro rats, deficient in AVP, had
low-level baseline AQP2 expression that was increased by
AVP administration. Taken together, these observations
demonstrate that AQP2 is responsible for the vasopressin-
dependent water permeability of the collecting duct.
Discovery of the Colton blood group antigen on AQP1
allowed the subsequent identification of rare Colton-null
individuals who lack AQP1. Surprisingly, these individuals
have no obvious clinical phenotype (Preston et al., 1994).
However, targeted gene disruption of the Aqp1 gene in
mice has demonstrated a marked urinary concentrating
defect (Ma et al., 1998), adding credence to the speculation
that the rare AQP1-null humans have an unidentified form
of compensation. In contrast to genetically AQP1-deficient
humans, AQP2 deficiency produces a dramatic clinical
phenotype. Nephrogenic diabetes insipidus (NDI) is a
disease whose aetiology is renal resistance to AVP and
whose clinical hallmark is excretion of large volumes of
dilute urine. Deen et al. (1994) described a single patient
with autosomal recessive NDI who was a compound
heterozygote for mutations in the AQP2 gene; additional
patients have recently been described. Mutant AQP2
proteins expressed in X. laevis oocytes did not form
functional water channels, owing to a defect in trafficking
to the oocyte plasma membrane (reviewed in King and
Agre, 1996).
Acquired nephrogenic diabetes insipidus is not uncom-
mon, and has a variety of causes. Nielsen and colleagues
have shown that lithium, bilateral ureteral obstruction,
and chronic hypokalaemia, known causes of NDI, all
produce marked reductions in AQP2 expression in
animals, with a concomitant decrease in urinary concen-
trating ability. More recently, increased AQP2 expression
has been demonstrated in conditions of fluid retention,
including congestive heart failure, cirrhosis and pregnancy.
As we gain insight into mechanisms regulating its function,
AQP2 may prove to be a therapeutic target in a variety of
circumstances of altered fluid balance.
Other aquaporins are also present in the nephron. AQP3
and AQP4 are expressed in the basolateral membrane of
the collecting duct epithelium, where it is likely they
4 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net
provide an exit pathway for fluid reabsorbed in the
collecting duct (reviewed in Agre et al., 1998). Disruption
of the Aqp4 gene in mice resulted in a mild urinary
concentrating defect. AQP3 transports glycerol as well as
water, but the functional significance of that observation is
unknown. AQP6 is also expressed in kidney, but its
subcellular location and physiological role have yet to be
identified.
Respiratory tract
The fluid requirements of the respiratory tract are complex.
In distal lung, removal of fluid in the perinatal period is a
critical step in the transition from placental gas exchange to
ex utero life. Throughout life, appropriate disposition of
water through the vascular, interstitial and airspace
compartments of the lung is critical to normal gas exchange
and lung defence. In the airways, strict regulation of the
airway surface liquid is essential for effective mucociliary
transport. In both the airways and nasopharynx, inspired
air must be humidified to prevent drying of the distal
airways, and water must be extracted from the expired air
stream to minimize breath-to-breath water loss.
Four water channels have been identified in the
respiratory tract (reviewed in Agre et al., 1998). In rat
lung, AQP1 is abundant in the apical and basolateral
membrane of endothelial cells in peribronchial vessels and
visceral pleura, and the venous sinusoids of the nasal
turbinates. AQP1 is minimally present in alveolar capil-
laries, and not present in airway epithelium. AQP5 is
expressed in the apical membrane of type I pneumocytes,
as well as in the apical membrane of secretory cells in
submucosal glands of the airways and nasopharynx. AQP3
is expressed in basal cells in tracheal and nasopharyngeal
epithelium, and in the basolateral membrane of columnar
cells in the nasal conchus epithelium. AQP4 is present in
the basolateral membrane of columnar cells of bronchial,
tracheal and nasopharyngeal epithelium. The nonoverlap-
ping distribution of water channels in the respiratory tract
probably provides a coordinated network of pathways for
transcellular water movement. The absence of known
water channels in the apical membrane of airway
epithelium is provocative, however. Clearly, undiscovered
aquaporins may exist in that location. Alternatively,
transcellular water movement might not occur at all points
across the respiratory epithelium but instead take place
only at select sites.
The phenomenon of perinatal lung water clearance is
well described. In that context, the ontogeny of aquaporins
in lung is of considerable interest. AQP1 is expressed in
fetal rat lung late in gestation, increases dramatically at
birth, and is sustained at high levels in adult animals.
Corticosteroids induce AQP1 expression in fetal (and
adult) rat lung, consistent with known acceleration of fetal
lung maturation by corticosteroids. AQP5 is expressed 1–2

days after birth in rat lung, with high-level expression in
adult animals. In contrast to AQP1, AQP5 is not induced
by corticosteroids. AQP4 exhibits transient high level
expression in distal lung 2 days after birth. While these
observations predict participation of water channels in
perinatal lung water clearance, their precise roles in this
process and in the pathophysiology of the premature lung
remain to be determined.
The distribution of aquaporins in the respiratory tract
suggests involvement in a variety of pathophysiological
processes. Altered expression or function of AQP1 and
AQP5 in distal lung may play a role in the pathogenesis of
pulmonary oedema. In an isolated sheep lung, water
transport out of the alveolar space was inhibited by
mercury, suggesting functional water channels at an
undefined anatomical level in the pathway from blood to
alveolus. In rat lung, water movement across the vascular
endothelium was inhibited by mercury; AQP1 was
identified in these vessels in endothelial caveolae. Abun-
dant expression of AQP1 in the visceral pleura predicts a
role in pleural fluid formation. Altered hydration of airway
secretions is an integral part of cystic fibrosis, probably
plays a role in facilitating normal mucociliary transport,
and may be a part of the pathogenesis of some forms of
asthma. In the nasopharynx, rhinorrhoea and congestion
are all too familiar complications of viral infections and
allergic rhinitis. The distribution of AQP1, AQP3, AQP4
and AQP5 in the respiratory tract portends their involve-
ment in some or all of these processes.
Brain
The physical constraints of the bony cranium mandate
tight regulation of intracranial fluid. Cerebrospinal fluid is
made by the choroid plexus, a specialized structure located
in the walls of the lateral, third and fourth ventricles
consisting of a vascular core covered by a secretory
epithelium. Immunolocalization studies demonstrated
that AQP1 is abundant in apical membrane microvilli of
the choroid epithelium; it is expressed there from early
gestation in the fetal rat. Colocalization of AQP1 with an
Na 1 /K 1 ATPase in the apical membrane strongly
suggests a role in cerebrospinal fluid production (reviewed
in King and Agre, 1996).
AQP4 was cloned from both lung and brain cDNA
libraries, although brain appears to be its predominant
distribution (reviewed in Agre et al., 1998). AQP4 is
expressed in the foot processes of astroglial cells, specifi-
cally in the perivascular membrane, suggesting a role in
regulation of extravascular brain water. Additionally,
AQP4 is abundant in lamellae adjacent to magnocellular
cells in the supraoptic and paraventricular nuclei, the site of
arginine vasopressin release. The AQP4-containing lamel-
lar structures may participate in the sensation and/or
transduction of osmotic signals to the magnocellular cells.
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Water Channels
Recent studies demonstrated a marked reduction of
AQP4-mediated water permeability by phorbol diesters.
Phosphorylation-mediated channel gating or trafficking
could provide a means for rapidly changing intracerebral
membrane water permeability.
Eye
Five aquaporins have been identified in nonoverlapping
domains in the eye. MIP comprises 50% of the lens fibre
cell protein, and has recently been shown to function as a
low-capacity water channel. Two different mutations of
the MIP gene in mice lead to congenital cataracts (reviewed
in Agre et al., 1998). The semidominant genetics of these
mutations are also consistent with a proposed structural
role for MIP in the lens. AQP1 in the corneal endothelium
and lens anterior epithelium, as well as AQP5 in the corneal
epithelium, may participate in reducing the water content
of those tissues, an important component of maintaining
transparency of the cornea and lens. Expression of AQP1
in the anterior ciliary epithelium and canals of Schlemm
suggests a role in secretion and uptake of aqueous humour.
AQP1 is also present in the iris, where high water
permeability is thought to facilitate the rapid shape
changes that occur with pupillary constriction. The
presence of AQP4 in the endfeet of Müller cells in the
retina predicts a role in the light-dependent hydration of
the space around photoreceptors. Finally, AQP3 in the
bulbar conjunctiva may play a role in hydration of the
protective covering of the eye.
Red blood cells
Red blood cells (RBCs) were the source for the initial
identification and purification of AQP1. While water
channels are thought to facilitate red cell survival during
the transit through the hypertonic renal medulla, geneti-
cally AQP1-deficient humans are not anaemic and have
evidence of only low-grade haemolysis. Recent identifica-
tion of low-level expression of AQP3 in RBCs, as well as
proposed washout of the medullary interstitial gradient,
may partially explain the surprisingly normal red cell
survival in the AQP1-null humans.
Salivary and lacrimal glands
AQP5 was cloned from a salivary gland library, and is
similar to the other aquaporins in water transport capacity.
AQP5 is abundantly expressed in the apical membrane of
secretory cells in salivary and lacrimal glands, but is not
present in the basolateral membrane or in duct cells
(reviewed in King and Agre, 1996). AQP5 has a protein
kinase A (PKA) consensus in a cytoplasmic loop similar to
that of AQP2. Phosphorylation of the protein is an
appealing though as yet unproven explanation for the
5
 Water Channels
rapid onset of salivation and lacrimation in response to the
appropriate stimuli. Adenoviral-mediated transfer of the
AQP5 gene is being evaluated as a potential therapy for
damaged salivary glands.
Curiously, the distribution of AQP5 coincides almost
exactly with the organ involvement of Sjögren disease, an
immunologically mediated process causing dry eyes, dry
mouth and desiccation of tracheobronchial secretions. The
antigen(s) driving immune destruction of the involved
organs is unknown, but the coincidence of distribution
with AQP5 is provocative.
Nonmammalian aquaporins
Aquaporins have now been identified in all levels of life
back to prokaryotes. Calamita and colleagues identified
the first bacterial homologue, aqpZ, in E. coli. aqpZ is
upregulated by and confers a survival advantage in
hypotonic conditions (Calamita et al., 1998). E. coli also
contains another MIP family homologue, glpF, a glycerol
transporter with low water permeability. The dual expres-
sion of two MIP family proteins, a water channel and a
glycerol channel, has been observed in other bacteria as
well. Saccharomyces also contains two aquaporin genes; at
least one of the two genes forms a functional water channel.
As might be predicted by their dependence on local
environmental water, plants express numerous aquaporins
(Maurel, 1997). Arabidopsis thaliana contains at least 23
aquaporin homologues in the EST (expressed sequence
tag) library, and similar diversity probably exists in other
plants as well. Two main groups of plant water channels
have been identified: those that transport water across the
plasma membrane, and those that regulate intracellular
turgor. Additionally, aquaporins have been identified in
processes from germination to self-pollination. The
expanding biology of plant aquaporins holds promise for
future developments in agriculture and vegetation control.
Summary
Discovery of the aquaporin family of membrane proteins
has provided new insights into molecular mechanisms of
membrane water permeability. Conservation of aquapor-
ins from prokaryotes to mammals is consistent with the
central role water plays in all forms of life. Historically, the
focus of discussions on membrane permeability has been
solute transport. While it is clear that in general solute
transport provides the driving force for water movement,
the example of AQP2 mutations causing nephrogenic
diabetes insipidus demonstrates that under certain circum-
stances water channels may be rate limiting. Further
investigation of the structure, regulation and function of
aquaporins should greatly enhance our ability to both
6 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net
understand and manipulate membrane water permeabil-
ity.
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Further Reading
Chou CL, Ma T, Yang B, Knepper MA and Verkman AS (1998)
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duct of aquaporin-4 knockout mice. American Journal of Physiology
274: C549–554.
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Biological Chemistry 263: 15634–15642.
Jung, JS Jung JS, Preston GM, Smith BL, Guggino WB and Agre P
(1994) Molecular structure of the water channel through Aquaporin
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