Reactome | Aquaporin-mediated transport

Aquaporin-mediated transport

Stable Identifier

R-HSA-445717

Type

Pathway

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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Aquaporins (AQP's) are six-pass transmembrane proteins that form channels in membranes. Each monomer contains a central channel formed in part by two asparagine-proline-alanine motifs (NPA boxes) that confer selectivity for water and/or solutes. The monomers assemble into tetramers. During passive transport by Aquaporins most aquaporins (i.e. AQP0/MIP, AQP1, AQP2, AQP3, AQP4, AQP5, AQP7, AQP8, AQP9, AQP10) transport water into and out of cells according to the osmotic gradient across the membrane. Four aquaporins (the aquaglyceroporins AQP3, AQP7, AQP9, AQP10) conduct glycerol, three aquaporins (AQP7, AQP9, AQP10) conduct urea, and one aquaporin (AQP6) conducts anions, especially nitrate. AQP8 also conducts ammonia in addition to water.
AQP11 and AQP12, classified as group III aquaporins, were identified as a result of the genome sequencing project and are characterized by having variations in the first NPA box when compared to more traditional aquaporins. Additionally, a conserved cysteine residue is present about 9 amino acids downstream from the second NPA box and this cysteine is considered indicative of group III aquaporins. Purified AQP11 incorporated into liposomes showed water transport. Knockout mice lacking AQP11 had fatal cyst formation in the proximal tubule of the kidney. Exogenously expressed AQP12 showed intracellular localization. AQP12 is expressed exclusively in pancreatic acinar cells.
Aquaporins are important in fluid and solute transport in various tissues. During Transport of glycerol from adipocytes to the liver by Aquaporins, glycerol generated by triglyceride hydrolysis is exported from adipocytes by AQP7 and is imported into liver cells via AQP9. AQP1 plays a role in forming cerebrospinal fluid and AQP1, AQP4, and AQP9 appear to be important in maintaining fluid balance in the brain. AQP0, AQP1, AQP3, AQP4, AQP8, AQP9, and AQP11 play roles in the physiology of the hepatobiliary tract.
In the kidney, water and solutes are passed out of the bloodstream and into the proximal tubule via the slit-like structure formed by nephrin in the glomerulus. Water is reabsorbed from the filtrate during its transit through the proximal tubule, the descending loop of Henle, the distal convoluted tubule, and the collecting duct. Aquaporin-1 (AQP1) in the proximal tubule and the descending thin limb of Henle is responsible for about 90% of reabsorption (as estimated from mouse knockouts of AQP1). AQP1 is located on both the apical and basolateral surface of epithelial cells and thus transports water through the epithelium and back into the bloodstream. In the collecting duct epithelial cells have AQP2 on their apical surfaces and AQP3 and AQP4 on their basolateral surfaces to transport water across the epithelium. Vasopressin regulates renal water homeostasis via Aquaporins by regulating the permeability of the epithelium through activation of a signaling cascade leading to the phosphorylation of AQP2 and its translocation from intracellular vesicles to the apical membrane of collecting duct cells.
Here, three views of aquaporin-mediated transport have been annotated: a generic view of transport mediated by the various families of aquaporins independent of tissue type (Passive transport by Aquaporins), a view of the role of specific aquaporins in maintenance of renal water balance (Vasopressin regulates renal water homeostasis via Aquaporins), and a view of the role of specific aquaporins in glycerol transport from adipocytes to the liver (Transport of glycerol from adipocytes to the liver by Aquaporins).

Literature References

PubMed ID	Title	Journal	Year
16107722	Disruption of aquaporin-11 produces polycystic kidneys following vacuolization of the proximal tubule Verkman, A, Morishita, Y, Hara-chikuma, M, Takata, K, Ikeda, M, Kobayashi, K, Matsuzaki, T, Andoo, A, Ookawara, S, Yamamoto, T, Shimono, M, Matsuki, A, Ishibashi, K, Kusano, E, Sasaki, S	Mol Cell Biol	2005
17961083	A current view of the mammalian aquaglyceroporins Praetorius, J, Rojek, A, Fenton, RA, Nielsen, S, Frøkiaer, J	Annu Rev Physiol	2008
19096770	Discovery of the aquaporins and development of the field Carbrey, JM, Agre, P	Handb Exp Pharmacol	2009
15924268	The renal plumbing system: aquaporin water channels Nejsum, LN	Cell Mol Life Sci	2005
19448080	Aquaporins: translating bench research to human disease Verkman, AS	J Exp Biol	2009
17222168	Regulation and dysregulation of aquaporins in water balance disorders Kwon, TH, Nielsen, S, Agre, P, Frøkiaer, J	J Intern Med	2007
11773613	Aquaporins in the kidney: from molecules to medicine Marples, D, Knepper, MA, Kwon, TH, Nielsen, S, Agre, P, Frøkiaer, J	Physiol Rev	2002
15340377	From structure to disease: the evolving tale of aquaporin biology Kozono, D, Agre, P, King, LS	Nat Rev Mol Cell Biol	2004
15901243	Aquaporins: highways for cells to recycle water with the outside world Calamita, G	Biol Cell	2005
20224213	The role of a group III AQP, AQP11 in intracellular organelle homeostasis Kondo, S, Tanaka, Y, Ishibashi, K, Hara, S, Koike, S	J Med Invest	2009
15809071	Identification of a novel aquaporin, AQP12, expressed in pancreatic acinar cells Ko, SB, Kuwahara, M, Ishibashi, K, Rai, T, Uchida, S, Sasaki, S, Itoh, T	Biochem Biophys Res Commun	2005
16650285	Aquaporin-11: a channel protein lacking apparent transport function expressed in brain Praetorius, J, Tsunenari, T, Nielsen, S, Gorelick, DA, Agre, P	BMC Biochem	2006