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J.E. Hall, K. Németh–Cahalan, K. Kalman, A. Froger; Zinc Increases the Water Permeability of Aquaporin 0 . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4094.
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Zinc is found in retina and choroid, ciliary body, iris, optic nerve, sclera, cornea, and lens. Furthemore cataracts have been associated with zinc deficiency in fish. We previously reported that in oocytes, AQP0 water permeability increases with acid pH and that His40 is required for this increase. We have now investigated the effect of zinc (and other transitional metals) on AQP0 water permeability and determined which amino–acids may be necessary for zinc sensitivity.
We expressed AQPs and mutants in Xenopus oocytes and measured the water permeability in response to an osmotic challenge in the presence of 1 mM ZnCl2.
Zinc increased AQP0 water permeability by a factor of two and prevented any additional increase induced by acid pH. Two histidines (His40 and His122) in AQP0 external loops were crucial for the zinc effect, since the single mutants (AQP0/His40Cys or AQP0/His122Gln) were insensitive to zinc. There was no effect of zinc on AQP1, AQP4 or MIPfun (AQP0 from Fundulus Heteroclitus). We also tested several mutants of AQP1 and MIPfun with added external histidines and found that zinc did not increase their water permeability. Nickel, but not copper, had the same effect as zinc on AQP0 water permeability.
Two histidines must be present at a very precise orientation and distance from each other (12 Å) to allow any effect of zinc on AQP0 water permeability. We propose a model where zinc ions bind to the two external histidines and improve the water flow by orienting the molecules of water in the external vestibule. These results offer the possibility of a pharmacology able to manipulate the water permeability of the lens beneficially and may explain some of the conflicting effects of zinc on the opacity of the lens.
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