Aquaporins: translating bench research to human disease

Abstract

SummaryThere is considerable potential for translating knowledge of aquaporin structure, function and physiology to the clinic. One area is in aquaporin-based diagnostics. The discovery of AQP4 autoantibodies as a marker of the neuromyelitis optica form of multiple sclerosis has allowed precise diagnosis of this disease. Other aquaporin-based diagnostics are possible. Another area is in aquaporin-based genetics. Genetic diseases caused by loss-of-function mutations in aquaporins include nephrogenic diabetes insipidus and cataracts, and functionally significant aquaporin polymorphisms are beginning to be explored. Perhaps of greatest translational potential is aquaporin-based therapeutics. Information largely from aquaporin knockout mice has implicated key roles of aquaporin-facilitated water transport in transepithelial fluid transport (urinary concentrating, gland fluid secretion), water movement into and out of the brain, cell migration (angiogenesis, tumor metastasis, wound healing) and neural function (sensory signaling, seizures). A subset of aquaporins that transport both water and glycerol, the 'aquaglyceroporins', regulate glycerol content in epidermal, fat and other tissues, and are involved in skin hydration, cell proliferation, carcinogenesis and fat metabolism. Aquaporin-based modulator drugs are predicted to be of broad potential utility in the treatment of edematous states, cancer, obesity, wound healing, epilepsy and glaucoma. These exciting possibilities and their associated challenges are reviewed.

The NPC Motif of Aquaporin-11, Unlike the NPA Motif of Known Aquaporins, Is Essential for Full Expression of Molecular Function

“…Similarly to AQP0, it has also been reported that each AQP4 tetramer interacts with four tetramers in the opposing membrane (29). Although the pathophysiological significance of this structure of AQP4 is still not clear (30), it is suggested that the structure mediates AQP4-dependent adhesion. We do not know whether this is the case for AQP11, but it is considered that the correct tertiary and/or quaternary structure of AQP11 is necessary for a structural role of the molecule inside or/and outside cells and that this role may be important for the function of hAQP11 in zebrafish.…”

Real-Time Monitoring of Changes in Brain Extracellular Sodium and Potassium Concentrations and Intracranial Pressure after Selective Vasopressin-1a Receptor Inhibition following Focal Traumatic Brain Injury in Rats

“…AQP4 is the predominant water channel in the brain and has a significant role in the pathophysiology of brain edema. [32][33][34][35][36] Evidence suggests V1aR regulate the expression and function of AQP4, 17,22,37 although the mechanism is still elusive. 17,22,[29][30][31] Recently, we explored the hypothesis that selective V1aR inhibition by the non-peptide antagonist SR49059 30,38 can reduce brain edema in animal models of middle cerebral artery occlusion 22,39 and TBI.…”

Homozygosity for aquaporin 7 G264V in three unrelated children with hyperglyceroluria and a mild platelet secretion defect

“…2 AQPs are classified, according to their sequence homology and permeability, into three subfamilies: (i) the water-specific "classical" AQPs, (ii) the aquaglyceroporins, and (iii) the unorthodox AQPs. 4 , [8][9][10][11] The aquaglyceroporin subfamily transports glycerol in addition to water because of the presence of an aspartic residue near the second NPA box, resulting in expansion of the pore to accept a larger molecule such as glycerol. The four subtypes of the aquaglyceroporin subfamily are: AQP3, AQP7, AQP9, and AQP10 (reviewed in refs.…”