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AQP2 Membrane Protein Introduction

Introduction of AQP2

AQP2 (aquaporin-2), encoded by AQP2 gene, is a member of the aquaporin family. Along with several other members, AQP2 gene is clustered together on chromosome 12q13. AQP2 is mainly expressed in the renal collecting duct epithelial cells and in intracellular vesicles located throughout the cell, where AQP2 participates in the reabsorption of water molecules from the urine by the renal collecting duct. Abnormal function or mutations of AQP2 have been linked to autosomal dominant and recessive forms of nephrogenic diabetes insipidus or kidney cyst.

Basic Information of AQP2
Protein Name Aquaporin-2
Gene Name AQP2
Aliases ADH water channel, Aquaporin-CD, AQP-CD, Collecting duct water channel protein
WCH-CD, Water channel protein for renal collecting duct
Organism Homo sapiens (Human)
UniProt ID P41181
Transmembrane Times 6
Length (aa) 271
Sequence MWELRSIAFSRAVFAEFLATLLFVFFGLGSALNWPQALPSVLQIAMAFGLGIGTLVQALGHISGAHINPAVTVACLVGCHVSVLRAAFYVAAQLLGAVAGAALLHEITPADIRGDLAVNALSNSTTAGQAVTVELFLTLQLVLCIFASTDERRGENPGTPALSIGFSVALGHLLGIHYTGCSMNPARSLAPAVVTGKFDDHWVFWIGPLVGAILGSLLYNYVLFPPAKSLSERLAVLKGLEPDTDWEEREVRRRQSVELHSPQSLPRGTKA

Function of AQP2 Membrane Protein

V2R and AQP2 are the major regulators of urine concentration. Phosphorylated by cAMP-dependent protein kinase PKA, AQP2 can move to the apical membrane, which causes water to be reabsorbed from the urine through the AQP2 water channel, thereby improving the body's dehydration state. It has shown that several serine, mainly include 256 (S256), 261 (S261) and 269 (S269) residing in the C-terminal of AQP2, have been identified as major phosphorylation sites associated with AQP2 trafficking. Mutations in AQP2 are associated with multiple diseases, such as Diabetes Insipidus, Nephrogenic, Autosomal and Diabetes Insipidus, Nephrogenic, X-Linked phenotype. Measuring urinary excretion of AQP2 is of value in diagnosing central diabetes insipidus. Innocuous nephrogenic diabetes insipidus (NDI) patients do not respond to vasopressin kidneys or AQP2 dysfunction can impair AQP2 activity and water reabsorption, leading to polyuria.

The mechanisms of urine concentration by vasopressin. Fig.1 The mechanisms of urine concentration by vasopressin.

The mechanisms of urine concentration by Wnt5a. Fig.2 The mechanisms of urine concentration by Wnt5a.

Application of AQP2 Membrane Protein in Literature

  1. Ando F and Uchida S. Activation of AQP2 water channels without vasopressin: therapeutic strategies for congenital nephrogenic diabetes insipidus. Clin Exp Nephrol. 2018, 22: 501-507. PubMed ID: 29478202

    In this article, the authors conduct an overview of novel therapeutic molecules of congenital nephrogenic diabetes insipidus (NDI). These molecules can activate AQP2 by bypassing defective V2R signaling with a particular focus on the activators of the calcium and cAMP signaling pathways.

  2. Ando F., et al. AKAPs-PKA disruptors increase AQP2 activity independently of vasopressin in a model of nephrogenic diabetes insipidus. Nat Commun. 2018, 9: 1411. PubMed ID: 29650969

    This article indicates that the low molecular weight compound 3,3'-diamino-4,4'-dihydroxydiphenylmethane (FMP-API-1) and its derivatives can increase AQP2 activity to the same extent as vasopressin, and increase urine osmolality in the context of V2R inhibition, suggesting that FMP-API-1 may be a promising therapy for the treatment of congenital NDI caused by V2R mutations.

  3. Noitem R., et al. Steviol slows renal cyst growth by reducing AQP2 expression and promoting AQP2 degradation. Biomed Pharmacother. 2018, 101: 754-762. PubMed ID: 29524884

    This article firstly shows that steviol can slow cyst growth by reducing AQP2 transcription, and promote proteasome, as well as lysosome-mediated AQP2 degradation.

  4. Miyazawa Y., et al. AQP2 in human urine is predominantly localized to exosomes with preserved water channel activities. Clin Exp Nephrol. 2018, 22(4):782-788. PubMed ID: 29396622

    This article reveals that AQP2 is a key molecule that determines the urine concentrating ability of the kidney. AQP2 is deeply involved in water-balance disorders such as water retention in heart failure and liver cirrhosis, indicating that it could be a useful biomarker for diagnosis and prognosis of such diseases.

  5. Ranieri M., et al. CaSR signaling down-regulates AQP2 expression via a novel microRNA pathway in pendrin and NaCl cotransporter knockout mice. FASEB J. 2018, 32: 2148-2159. PubMed ID: 29212817

    This report shows that CaSR signaling can reduce AQP2 abundance both via AQP2-targeting miRNA-137 and the p38-MAPK/AQP2-pS261/ubiquitination/proteasomal axis.

AQP2 Preparation Options

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Reference

  1. Ando F and Uchida S. (2018). Activation of AQP2 water channels without vasopressin: therapeutic strategies for congenital nephrogenic diabetes insipidus. Clin Exp Nephrol. 22, 501-507.

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