Aquaporin-2 Explained

Aquaporin-2 (AQP-2) is found in the apical cell membranes of the kidney's collecting duct principal cells and in intracellular vesicles located throughout the cell. It is encoded by the gene.

Regulation

It is the only aquaporin regulated by vasopressin.^[1] The basic job of aquaporin 2 is to reabsorb water from the urine while its being removed from the blood by the kidney. Aquaporin 2 is in kidney epithelial cells and usually lies dormant in intracellular vesicle membranes. When it is needed, vasopressin binds to the cell surface vasopressin receptor thereby activating a signaling pathway that causes the aquaporin 2 containing vesicles to fuse with the plasma membrane, so the aquaporin 2 can be used by the cell.^[2] This aquaporin is regulated in two ways by the peptide hormone vasopressin:

• short-term regulation (minutes) through trafficking of AQP2 vesicles to the apical region where they fuse with the apical plasma membrane
• long-term regulation (days) through an increase in AQP2 gene expression.

This aquaporin is also regulated by food intake. Fasting reduces expression of this aquaporin independently of vasopressin.

Clinical significance

Mutations in this channel are associated with nephrogenic diabetes insipidus, which can be autosomal dominant or recessive. Mutations in the vasopressin receptor cause a similar X-linked phenotype.

Lithium, which is often used to treat bipolar disorder, can cause acquired diabetes insipidus (characterized by the excretion of large volumes of dilute urine) by decreasing the expression of the AQP2 gene.

The expression of the AQP2 gene is increased during conditions associated with water retention such as pregnancy and congestive heart failure.

See also

• Aquaporin

Further reading

• Bichet DG . Nephrogenic diabetes insipidus . Advances in Chronic Kidney Disease . 13 . 2 . 96–104 . April 2006 . 16580609 . 10.1053/j.ackd.2006.01.006 . https://web.archive.org/web/20180718235218/http://discovery.ucl.ac.uk/1540833/1/Bockenhauer_Bichet%252011%2520janv%25202017%2520references%2520in%2520sequence%2520MOP290219%2520Bichet%2520MS%255B1%255D.pdf . dead . 2018-07-18 .
• Bouley R, Hasler U, Lu HA, Nunes P, Brown D . Bypassing vasopressin receptor signaling pathways in nephrogenic diabetes insipidus . Seminars in Nephrology . 28 . 3 . 266–78 . May 2008 . 18519087 . 2494582 . 10.1016/j.semnephrol.2008.03.010 .
• Robben JH, Knoers NV, Deen PM . Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus . American Journal of Physiology. Renal Physiology . 291 . 2 . F257–70 . August 2006 . 16825342 . 10.1152/ajprenal.00491.2005 . 2066/50267 . 15392 . free .
• Sasaki S, Fushimi K, Saito H, Saito F, Uchida S, Ishibashi K, Kuwahara M, Ikeuchi T, Inui K, Nakajima K . Cloning, characterization, and chromosomal mapping of human aquaporin of collecting duct . The Journal of Clinical Investigation . 93 . 3 . 1250–6 . March 1994 . 7510718 . 294077 . 10.1172/JCI117079 .
• Deen PM, Weghuis DO, Sinke RJ, Geurts van Kessel A, Wieringa B, van Os CH . Assignment of the human gene for the water channel of renal collecting duct Aquaporin 2 (AQP2) to chromosome 12 region q12→q13 . Cytogenetics and Cell Genetics . 66 . 4 . 260–2 . 1994 . 7512890 . 10.1159/000133707 .
• Uchida S, Sasaki S, Fushimi K, Marumo F . Isolation of human aquaporin-CD gene . The Journal of Biological Chemistry . 269 . 38 . 23451–5 . September 1994 . 10.1016/S0021-9258(17)31537-5 . 7522228 . free .
• van Lieburg AF, Verdijk MA, Knoers VV, van Essen AJ, Proesmans W, Mallmann R, Monnens LA, van Oost BA, van Os CH, Deen PM . Patients with autosomal nephrogenic diabetes insipidus homozygous for mutations in the aquaporin 2 water-channel gene . American Journal of Human Genetics . 55 . 4 . 648–52 . October 1994 . 7524315 . 1918308 .
• Saito F, Sasaki S, Chepelinsky AB, Fushimi K, Marumo F, Ikeuchi T . Human AQP2 and MIP genes, two members of the MIP family, map within chromosome band 12q13 on the basis of two-color FISH . Cytogenetics and Cell Genetics . 68 . 1–2 . 45–8 . 1994 . 7525161 . 10.1159/000133885 .
• Nielsen S, Chou CL, Marples D, Christensen EI, Kishore BK, Knepper MA . Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane . Proceedings of the National Academy of Sciences of the United States of America . 92 . 4 . 1013–7 . February 1995 . 7532304 . 42627 . 10.1073/pnas.92.4.1013 . 1995PNAS...92.1013N . free .
• Brown D . The ins and outs of aquaporin-2 trafficking . American Journal of Physiology. Renal Physiology . 284 . 5 . F893–901 . May 2003 . 12676734 . 10.1152/ajprenal.00387.2002 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Deen PM, Verdijk MA, Knoers NV, Wieringa B, Monnens LA, van Os CH, van Oost BA . Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine . Science . 264 . 5155 . 92–5 . April 1994 . 8140421 . 10.1126/science.8140421 . 1994Sci...264...92D .
• Oksche A, Möller A, Dickson J, Rosendahl W, Rascher W, Bichet DG, Rosenthal W . Two novel mutations in the aquaporin-2 and the vasopressin V2 receptor genes in patients with congenital nephrogenic diabetes insipidus . Human Genetics . 98 . 5 . 587–9 . November 1996 . 8882880 . 10.1007/s004390050264 . 27581991 .
• Mulders SM, Knoers NV, Van Lieburg AF, Monnens LA, Leumann E, Wühl E, Schober E, Rijss JP, Van Os CH, Deen PM . New mutations in the AQP2 gene in nephrogenic diabetes insipidus resulting in functional but misrouted water channels . Journal of the American Society of Nephrology . 8 . 2 . 242–8 . February 1997 . 10.1681/ASN.V82242 . 9048343 . 2066/24513 . free .
• Ma T, Yang B, Umenishi F, Verkman AS . Closely spaced tandem arrangement of AQP2, AQP5, and AQP6 genes in a 27-kilobase segment at chromosome locus 12q13 . Genomics . 43 . 3 . 387–9 . August 1997 . 9268644 . 10.1006/geno.1997.4836 .
• Canfield MC, Tamarappoo BK, Moses AM, Verkman AS, Holtzman EJ . Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response . Human Molecular Genetics . 6 . 11 . 1865–71 . October 1997 . 9302264 . 10.1093/hmg/6.11.1865 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Vargas-Poussou R, Forestier L, Dautzenberg MD, Niaudet P, Déchaux M, Antignac C . Mutations in the vasopressin V2 receptor and aquaporin-2 genes in 12 families with congenital nephrogenic diabetes insipidus . Journal of the American Society of Nephrology . 8 . 12 . 1855–62 . December 1997 . 10.1681/ASN.V8121855 . 9402087 . free .
• Kuwahara M . Aquaporin-2, a vasopressin-sensitive water channel, and nephrogenic diabetes insipidus . Internal Medicine . 37 . 2 . 215–7 . February 1998 . 9550615 . 10.2169/internalmedicine.37.215 . free .
• Mulders SM, Bichet DG, Rijss JP, Kamsteeg EJ, Arthus MF, Lonergan M, Fujiwara M, Morgan K, Leijendekker R, van der Sluijs P, van Os CH, Deen PM . An aquaporin-2 water channel mutant which causes autosomal dominant nephrogenic diabetes insipidus is retained in the Golgi complex . The Journal of Clinical Investigation . 102 . 1 . 57–66 . July 1998 . 9649557 . 509065 . 10.1172/JCI2605 .
• Goji K, Kuwahara M, Gu Y, Matsuo M, Marumo F, Sasaki S . Novel mutations in aquaporin-2 gene in female siblings with nephrogenic diabetes insipidus: evidence of disrupted water channel function . The Journal of Clinical Endocrinology and Metabolism . 83 . 9 . 3205–9 . September 1998 . 10.1210/jcem.83.9.5074 . 9745427 . 1074523 . free .
• Saito T, Ishikawa S, Ito T, Oda H, Ando F, Higashiyama M, Nagasaka S, Hieda M, Saito T . Urinary excretion of aquaporin-2 water channel differentiates psychogenic polydipsia from central diabetes insipidus . The Journal of Clinical Endocrinology and Metabolism . 84 . 6 . 2235–7 . June 1999 . 10.1210/jcem.84.6.5715 . 10372737 . free .

External links

• GeneReviews/NCBI/NIH/UW entry on Nephrogenic Diabetes Insipidus

Notes and References

1. Dibas AI, Mia AJ, Yorio T . Aquaporins (water channels): role in vasopressin-activated water transport . Proceedings of the Society for Experimental Biology and Medicine . 219 . 3 . 183–99 . December 1998 . 9824541 . 10.3181/00379727-219-44332 . 28952956 .
2. Book: Lodish . Harvey . Berk . Arnold . Kaiser . Chris A. . Krieger . Monty . Scott . Matthew P. . Bretscher . Anthony . Ploegh . Hidde . Matsudaira . Paul . vanc . Molecular Cell Biology . limited . 2008 . Freeman . New York . 978-0-7167-7601-7 . 445 . 6th .