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Title: Transmembrane water-flux through SLC4A11: A route defective in genetic corneal diseases
Authors: Vilas, G.L.
Loganathan, S.K.
Liu, J.
Riau, A.K.
Young, J.D.
Mehta, J.S. 
Vithana, E.N.
Casey, J.R.
Issue Date: Nov-2013
Citation: Vilas, G.L., Loganathan, S.K., Liu, J., Riau, A.K., Young, J.D., Mehta, J.S., Vithana, E.N., Casey, J.R. (2013-11). Transmembrane water-flux through SLC4A11: A route defective in genetic corneal diseases. Human Molecular Genetics 22 (22) : 4579-4590. ScholarBank@NUS Repository.
Abstract: Three genetic corneal dystrophies [congenital hereditary endothelial dystrophy type 2 (CHED2), Harboyan syndromeand Fuchs endothelial corneal dystrophy] arise from mutations of the SLC4a11 gene, which cause blindnessfrom fluid accumulation in the corneal stroma. Selective transmembrane water conductance controls cellsize, renal fluid reabsorption and cell division. All known water-channelling proteins belong to themajor intrinsicprotein family, exemplified by aquaporins (AQPs). Here we identified SLC4A11, a member of the solute carrierfamily 4 of bicarbonate transporters, as an unexpected addition to known transmembrane watermovement facilitatorsThe rate of osmotic-gradient driven cell-swelling was monitored in Xenopus laevis oocytes and HEK293cells,expressinghumanAQP1, NIP5;1 (awaterchannelproteinfromplant),hCNT3(ahumannucleosidetransporter)andhumanSLC4A11.hCNT3-expressingcellsswellednofaster thancontrolcells,whereasSLC4A11-mediatedwaterpermeationat a rateabouthalf thatof someAQPproteins.SLC4A11-mediatedwatermovementwas: (i) similartosomeAQPsinrate; (ii)uncoupledfromsolute-flux; (iii) inhibitedbystilbenedisulfonates(classicalSLC4inhibitors);(iv) inactivated in one CHED2 mutant (R125H). Localization of AQP1 and SLC4A11 in human and murinecorneal (apical and basolateral, respectively) suggests a cooperative role inmediating trans-endothelial water reabsorption.Slc4a112/2 mice manifest corneal oedema and distorted endothelial cells, consistent with loss of awater-flux. Observed water-flux through SLC4A11 extends the repertoire of known water movement pathwaysand call for a re-examination of explanations for water movement in human tissues. © The Author 2013. Published by Oxford University Press. All rights reserved.
Source Title: Human Molecular Genetics
ISSN: 09646906
DOI: 10.1093/hmg/ddt307
Appears in Collections:Staff Publications

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