Aquaporins (AQPs) are membrane water channels which facilitate osmotic water transport across cell membranes (water homeostasis). In addition to water, AQPs facilitate the transport of other small uncharged molecules, such as urea, glycerol, NH3, CO2, and H2O2. AQPs are impermeable to protons, and can therefore preserve pH gradients. AQPs are hydrophobic proteins consisting of six membrane-spanning alpha-helices, and the water-transporting pore is functional only when four AQP monomers form a tetramer.
Aquaporins are regulated by phosphorylation, glycolysation, ubiquitination, and by interaction with other proteins. AQP function is also regulated by intracellular trafficking.
In humans, 13 AQPs have been characterized (AQP0-AQP12); altogether over 300 AQPs have been identified in procaryotes and eukaryotes. AQPs have different substrate specificity - AQP0, AQP1, AQP2, AQP4, AQP5, and AQP8 work mainly as water channels, while AQP3 facilitates the transport of glycerol and water, and AQP7 and ACP10 transport also urea; AQP9 may be permeable to a wide range of solutes.
AQP0 is located in the fiber cells of eye lens.
AQP1 is found in most tissues, including the kidneys, brain, heart, lung, GI tract, liver, spleen, salivary glands, muscle, and erythrocytes. It is highly expressed in microvascular endothelial cells. In addition to water, AQP1 facilitates the transport of NH3, CO2, O2, NO, and even monovalent cations when activated by cGMP. Vasopressin increases the water permeability of AQP1, and atrial natriuretic peptide decreases it.
AQP2 is only permeable to water. It is found in the principal cells of collecting ducts of kidneys, in both apical plasma membrane and subapical vesicles. Vasopressin, ANP, NO, angiotensin II, and some other compounds regulate the expression, activation, and trafficking of AQP2.
AQP3 is found in most tissues, including the kidneys, heart, GI tract, respiratory tract, brain, fat tissue, skin, and erythrocytes. It facilitates the transport of water, glycerol, urea, and H2O2.
AQP4 is the predominant aquaporin of the CNS, but it is also found in the kidneys, heart, muscle, and GI tract. In the brain, AQP4 mainly exists in glial astrocytes, and it is an important part of the blood brain barrier and glymphatic system. It facilitates the transport of water and CO2. Histamine and vasopressin may regulate the translocation of AQP4. AQP4 may play a role in some neurological disorders, including oedema and epilepsy.
AQP5 is involved in generation of saliva, tears, and pulmonary secretions. In addition of secretory glands, alveolar epithelium, and eyes, it is also found in GI tract and kidneys. AQP5 facilitates the transport of water and CO2.
AQP6 is found intracellularly in the kidneys and brain. It facilitates the transport of urea, glycerol, and anions such as NO3-. Transport of water seems to be facilitated only at acidic pH, and also anionic permeability is increased in acidic pH. AQP6 may play a role in acid-base homeostasis.
AQP7 is abundantly expressed in white adipose tissue, where it facilitates the influx and efflux of glycerol. It is involved in metabolic disease and obesity. AQP7 is also found in kidneys, cardiac muscle, and skeletal muscle. In addition to water, it also transports water, urea, NH3, and NH4+. AQP7 is found in pancreatic β-cells, and it is the main glycerol channel in pancreas; glycerol uptake in β-cells leads to insulin release (Méndez-Giménez et al., 2017).
AQP8 is expressed in the liver, pancreas, lungs, and kidneys. It facilitates the transport of water, H2O2, urea, and NH4+. In the liver, during basal conditions, it is mainly located in mitochondria and vesicular compartment, but can be translocated to cell membrane.
AQP9 is found in the liver, spleen, adipocytes, brain, and white blood cells. It facilitates the transport of water, urea and other carbamides, glycerol, CO2, NH3, and H2O2. In the sinusoidal plasma membrane of hepatocytes it facilitates the efflux of urea. Glycerol transport in the liver is dependent on AQP9. In the brain, AQP9 participates in the transport of lactate and ketone bodies across the blood brain barrier. A short isoform of AQP9 is found on the inner membrane of mitochondria.
AQP10 is expressed in GI tract and adipocytes, where it facilitates the transport of water, glycerol, and urea.
AQP11 is expressed in heart, muscle, kidneys, GI tract, liver, brain, and white blood cells, possibly in endoplasmic reticulum.
AQP12 is found intracellularly in pancreatic acinar cells.
Other water transporters
Urea transporter B (UT-B) functions also as water transporter, with similar permeability as AQP1. Some cotransporters are also permeable to water, including K+-Cl- cotransporter, Na+-K+-Cl- cotransporter, Monocarboxylate transporter (MCT), GABA transporter, Na+-coupled glutamate transporter, Na+-glucose transporters, Na+-dicarboxylate cotransporter, and glucose transporters (GLUTs).
TGN-020 is a specific AQP1 and AQP4 inhibitor, which has been labelled with positron-emitting 11C (Nakamura et al., 2011; Suzuki et al., 2013). TGN-020 PET could differentiate between astrocytoma grades III and IV (Suzuki et al., 2018).
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Created at: 2017-08-08
Updated at: 2018-07-07
Written by: Vesa Oikonen