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Official Full Name
aquaporin 2 (collecting duct)
Aquaporin 2 (AQP2) is a water transport protein that forms water channels in kidney tubules and plays a predominant role in controlling organism water homeostasis. Members of the aquaporin family are multiple pass transmembrane proteins that form homotetr
AQP2; aquaporin 2 (collecting duct); aquaporin-2; AQP-2; aquaporin-CD; ADH water channel; water-channel aquaporin 2; collecting duct water channel protein; water channel protein for renal collecting duct; AQP-CD; WCH-CD; MGC34501; MIP; major intrinsic protein of lens fiber

Aquaporin-2 (AQP2) is a major target molecule of antidiuretic hormone (ADH). It regulates the water permeability of collecting ducts and plays an important role in urine concentration. Similar to other aquaporins, the three-dimensional structure of AQP2 is an "hourglass model" that exists as a tetramer in the cell membrane. Each monomer consists of one peptide chain, its N-terminus and the C-terminus are located on the cytoplasmic side of the cell membrane. The peptide chain consists of six long alpha helices on both sides of the membrane and 5 rings are connected (A-E loop). A monomer is a separate functional unit with a channel tube in the center. AQP2 is mainly composed of loop C and loop D to form a water molecule channel tube.

AQP2 is mainly expressed in the main cells of the renal collecting duct and is also expressed in the inner ear, male and female reproductive systems. AQP2 is distributed in the apical plasma membrane and vesicles near the apical plasma membrane in the main cells of the renal collecting duct. In recent years, AQP2 expression has also been found in renal cysts and polycystic kidney epithelial cells.

AQP2 Function

The most important function of AQP2 is to mediate transmembrane transport of water. AQP2 plays an important role in urine concentration and regulating the water balance of the human kidney. When the plasma osmotic pressure is increased, the neurohypophyseal releases ADH into the blood circulation, and binds to the V2 receptor (mainly distributed on the basal side of the main cell of the collecting duct), causing the AQP2-containing vesicles under the plasma membrane of the main cell to move toward the apical plasma membrane. Finally, the expression of apical plasma membrane AQP2 is increased and the ability of urine concentration is enhanced. In addition, there are a large number of V2 receptors and AQP2 expression in the inner ear cochlea and AQP2 plays an important role in regulating the inner lymphatic balance of the inner ear. Zhang et al. found AQP2 expression in female endometrium and vaginal mucosa epithelium, and AQP2 was associated with endometrial damage in the process of controlled ovarian stimulation during embryo transfer.

AQP2 Regulation Mechanism

The expression of AQP2 and "shuttle" are mainly regulated by ADH. ADH is secreted by the pituitary gland. The regulation of AQP2 by ADH mainly through two mechanisms: 1. short-term regulation: regulation of the distribution of AQP2 in the main cells of the collecting duct but the total amount of AQP2 in the cells is unchanged. Then the vesicles containing AQP2 are moved to the apical plasma membrane of the main cell, increasing the water permeability of the apical plasma membrane. 2. Long-term regulation: regulation of the total amount of AQP2 in the main cells of the collecting duct, increasing the transcription and translation level of AQP2.

Short-term adjustment

ADH binds to the V2 receptor and activates the adenylate cyclase (AC) near the cytoplasmic side of the cell membrane, hydrolyzing and cyclizing ATP to form a second messenger cAMP, thereby activating the cAMP/PKA signaling pathway. Then the AQP2-containing vesicles are moved to the apical plasma membrane. In addition, other protein kinases may also be involved, such as Akt, Sgk, myosin light chain kinase, CaM-dependent protein kinase, protein kinase C and the like. ADH regulates AQP2 with AQP2 phosphorylation. It has been found that four serines (Ser256, Ser261, Ser264, Ser269) on the AQP2 protein can be regulated by phosphorylation. PKA increased phosphorylation at Ser256, Ser264, and Ser269, and decreased phosphorylation at Ser261. Tamma et al. found that the phosphorylation of Ser256 increased the vesicles containing AQP2 to the apical plasma membrane. The phosphorylation of Ser261 could inhibit this process. The phosphorylation of Ser264 and Ser269 remains to be further studied. Sjöhamn et al. found that other protein kinases such as c-Jun amino terminal kinase, p38, cd1, cd5 reduced phosphorylation of Ser261. In addition, Sasaki et al. found that ADH bind to the V2 receptor and activated the G protein Gq, moving the AQP2-containing vesicles to the apical plasma membrane through the IP3-Ca2+ signaling pathway.

Figure 1. Identification of a PKA-independent pathway controlling AQP2 trafficking. Schematic model. ER, endoplasmic reticulum. (Tamma, et al. 2014).

Long-term adjustment

The newly produced AQP2 protein is transported from the endoplasmic reticulum to the membrane under the guidance of a signal peptide. It was previously thought that AQP2 was directly transported to the apical plasma membrane of the collecting duct, but Naofumi et al. observed the vesicles in the collecting duct cells by confocal microscopy at 4 °C. It was found that part of AQP2 moved to the basal side of the cell and then moved to the apical plasma membrane. The transport mechanism from the basal side to the apical plasma membrane is independent of Rab11.

ADH is not the only factor regulating AQP2 expression. Al et al. have found that Nitrogen monoxide (NO) can promote renal water reabsorption to increase the distribution ratio of AQP2 in the apical plasma membrane and vesicles of collecting duct cells. Ortiz et al. found that the decrease in the activity of Nitric oxide Synthase (NOS) caused a decrease in AQP2 expression in the apical plasma membrane of collecting duct cells. Studies have found that excessive urinary calcium concentration reduces the expression of AQP2 on the plasma membrane at the apical end of the collecting duct, which decreases the function of urine concentration.


  1. Zhang, D., Xu, G., Zhang, R., Zhu, Y., Gao, H., & Zhou, C., et al. (2014). Decreased expression of aquaporin 2 is associated with impaired endometrial receptivity in controlled ovarian stimulation. Reproduction Fertility & Development, 28(4), 499.
  2. Tamma, G., Lasorsa, D., Trimpert, C., Ranieri, M., Di, M. A., & Mola, M. G., et al. (2014). A protein kinase a-independent pathway controlling aquaporin 2 trafficking as a possible cause for the syndrome of inappropriate antidiuresis associated with polycystic kidney disease 1 haploinsufficiency. Journal of the American Society of Nephrology Jasn, 25(10), 2241.
  3. Sjöhamn, J., & Hedfalk, K. (2014). Unraveling aquaporin interaction partners. BBA-General Subjects, 1840(5), 1614-1623.
  4. Sasaki, S., Yui, N., & Noda, Y. (2014). Actin directly interacts with different membrane channel proteins and influences channel activities: aqp2 as a model. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1838(2), 514-520.
  5. Naofumi, Y., Lu, H. A. J., Ying, C., Naohiro, N., Richard, B., & Dennis, B. (2013). Basolateral targeting and microtubule-dependent transcytosis of the aquaporin-2 water channel. Am J Physiol Cell Physiol, 304(1), C38-C48.
  6. Al, T. S., Mose, F. H., Jensen, J. M., Bech, J. N., & Pedersen, E. B. (2014). Effect of vasopressin antagonism on renal handling of sodium and water and central and brachial blood pressure during inhibition of the nitric oxide system in healthy subjects. BMC Nephrology, 15(1), 1-12.
  7. Ortiz, M. C., Albertoni Borghese, M. F., Balonga, S. E., Lavagna, A., Filipuzzi, A. L., & Elesgaray, R., et al. (2014). Renal response to l-arginine in diabetic rats. a possible link between nitric oxide system and aquaporin-2. PLoS ONE, 9, 8(2014-8-11), 9(8), e104923.

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