TY - JOUR

T1 - Aquaporin 2 regulation

T2 - implications for water balance and polycystic kidney diseases

AU - Olesen, Emma T. B.

AU - Fenton, Robert A.

PY - 2021

Y1 - 2021

N2 - Aquaporin 2 has an essential role in water reabsorption in the collecting duct. Here, the authors discuss novel insights in the field of aquaporin 2 regulation and how they might have implications for the treatment not only of water balance disorders but also of patients with autosomal dominant polycystic kidney disease.Targeting the collecting duct water channel aquaporin 2 (AQP2) to the plasma membrane is essential for the maintenance of mammalian water homeostasis. The vasopressin V2 receptor (V2R), which is a G(S) protein-coupled receptor that increases intracellular cAMP levels, has a major role in this targeting process. Although a rise in cAMP levels and activation of protein kinase A are involved in facilitating the actions of V2R, studies in knockout mice and cell models have suggested that cAMP signalling pathways are not an absolute requirement for V2R-mediated AQP2 trafficking to the plasma membrane. In addition, although AQP2 phosphorylation is a known prerequisite for V2R-mediated plasma membrane targeting, none of the known AQP2 phosphorylation events appears to be rate-limiting in this process, which suggests the involvement of other factors; cytoskeletal remodelling has also been implicated. Notably, several regulatory processes and signalling pathways involved in AQP2 trafficking also have a role in the pathophysiology of autosomal dominant polycystic kidney disease, although the role of AQP2 in cyst progression is unknown. Here, we highlight advances in the field of AQP2 regulation that might be exploited for the treatment of water balance disorders and provide a rationale for targeting these pathways in autosomal dominant polycystic kidney disease.

AB - Aquaporin 2 has an essential role in water reabsorption in the collecting duct. Here, the authors discuss novel insights in the field of aquaporin 2 regulation and how they might have implications for the treatment not only of water balance disorders but also of patients with autosomal dominant polycystic kidney disease.Targeting the collecting duct water channel aquaporin 2 (AQP2) to the plasma membrane is essential for the maintenance of mammalian water homeostasis. The vasopressin V2 receptor (V2R), which is a G(S) protein-coupled receptor that increases intracellular cAMP levels, has a major role in this targeting process. Although a rise in cAMP levels and activation of protein kinase A are involved in facilitating the actions of V2R, studies in knockout mice and cell models have suggested that cAMP signalling pathways are not an absolute requirement for V2R-mediated AQP2 trafficking to the plasma membrane. In addition, although AQP2 phosphorylation is a known prerequisite for V2R-mediated plasma membrane targeting, none of the known AQP2 phosphorylation events appears to be rate-limiting in this process, which suggests the involvement of other factors; cytoskeletal remodelling has also been implicated. Notably, several regulatory processes and signalling pathways involved in AQP2 trafficking also have a role in the pathophysiology of autosomal dominant polycystic kidney disease, although the role of AQP2 in cyst progression is unknown. Here, we highlight advances in the field of AQP2 regulation that might be exploited for the treatment of water balance disorders and provide a rationale for targeting these pathways in autosomal dominant polycystic kidney disease.

KW - VASOPRESSIN-MEDIATED TRANSLOCATION

KW - DEPENDENT PROTEIN-KINASE

KW - THICK ASCENDING LIMB

KW - CYST GROWTH

KW - DIABETES-INSIPIDUS

KW - CYCLIC-AMP

KW - F-ACTIN

KW - MOLECULAR-MECHANISMS

KW - APICAL MEMBRANE

KW - ANGIOTENSIN-II

U2 - 10.1038/s41581-021-00447-x

DO - 10.1038/s41581-021-00447-x

M3 - Review

C2 - 34211154

VL - 17

SP - 765

EP - 781

JO - Nature Reviews Nephrology

JF - Nature Reviews Nephrology

SN - 1759-5061

ER -