CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
Functional Assessment of SLC4A11, an Integral Membrane Protein Mutated in Corneal Dystrophies
SAMPATH K. LOGANATHAN; HANS-PETER SCHNEIDER; JOACHIM W. DEITMER; JOSEPH CASEY; PATRICIO E. MORGAN
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
AMER PHYSIOLOGICAL SOC
Lugar: Bethesda; Año: 2016
SLC4A11,a member of the SLC4 family of bicarbonate transporters, is a widely expressedintegral membrane protein, abundant in kidney and cornea. Mutations of SLC4A11cause some cases of the blinding corneal dystrophies, congenital hereditaryendothelial dystrophy and Fuchs endothelial corneal dystrophy. These diseasesare marked by fluid accumulation in the corneal stroma, secondary to defectivefluid reabsorption by the corneal endothelium. The role of SLC4A11 in thesecorneal dystrophies is not firmly established, as SLC4A11 function remainsunclear. To clarify the normal function(s) of SLC4A11, we characterized theprotein following expression in the simple, low-background, expression system, X. laevis oocytes. Since plant andfungal SLC4A11 orthologs transport borate, we measured cell swelling associatedwith accumulation of solute, borate. The plant water/borate transporter,Nip5;1, manifested borate transport, whereas human SLC4A11 did not. SLC4A11supported osmotically-driven water accumulation that was electroneutral and Na+-independent.Studies in oocytes and HEK293 cells could not detect Na+-coupled HCO3-transport or Cl-/HCO3- exchange by SLC4A11. SLC4A11mediated electroneutral NH3 transport in oocytes. Voltage-dependentOH- or H+ movement was not measurable in SLC4A11 expressingoocytes, but SLC4A11-expressing HEK293 cells manifested low level cytosolicacidification at baseline. In mammalian cells, but not oocytes, OH-/H+conductance may arise when SLC4A11 activates another protein or itself isactivated by another protein. These data argue against a role of human SLC4A11in bicarbonate or borate transport. This work provides additional support forwater and ammonia transport by SLC4A11. When expressed in oocytes, SLC4A11transported NH3, not NH3/H+.