Functional assessment of SLC4A11, an integral membrane protein mutated in corneal dystrophies

SLC4A11, a member of the SLC4 family of bicarbonate transporters, is a widely expressed integral membrane protein, abundant in kidney and cornea. Mutations of SLC4A11 cause some cases of the blinding corneal dystrophies, congenital hereditary endothelial dystrophy, and Fuchs endothelial corneal dyst...

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Autores principales: Loganathan, Sampath K., Schneider, Hans Peter, Morgan, Patricio Eduardo, Deitmer, Joachim W., Casey, Joseph R.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2016
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Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/99458
https://ri.conicet.gov.ar/11336/54183
https://www.physiology.org/doi/10.1152/ajpcell.00078.2016
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5130586/
Aporte de:
id I19-R120-10915-99458
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Exactas
Química
Ciencias Médicas
Ammonia
Corneal dystrophy
Endothelial cell
SLC4A11
Water flux
spellingShingle Ciencias Exactas
Química
Ciencias Médicas
Ammonia
Corneal dystrophy
Endothelial cell
SLC4A11
Water flux
Loganathan, Sampath K.
Schneider, Hans Peter
Morgan, Patricio Eduardo
Deitmer, Joachim W.
Casey, Joseph R.
Functional assessment of SLC4A11, an integral membrane protein mutated in corneal dystrophies
topic_facet Ciencias Exactas
Química
Ciencias Médicas
Ammonia
Corneal dystrophy
Endothelial cell
SLC4A11
Water flux
description SLC4A11, a member of the SLC4 family of bicarbonate transporters, is a widely expressed integral membrane protein, abundant in kidney and cornea. Mutations of SLC4A11 cause some cases of the blinding corneal dystrophies, congenital hereditary endothelial dystrophy, and Fuchs endothelial corneal dystrophy. These diseases are marked by fluid accumulation in the corneal stroma, secondary to defective fluid reabsorption by the corneal endothelium. The role of SLC4A11 in these corneal dystrophies is not firmly established, as SLC4A11 function remains unclear. To clarify the normal function(s) of SLC4A11, we characterized the protein following expression in the simple, low-background expression system <i>Xenopus laevis</i> oocytes. Since plant and fungal SLC4A11 orthologs transport borate, we measured cell swelling associated with accumulation of solute borate. The plant water/borate transporter NIP5;1 manifested borate transport, whereas human SLC4A11 did not. SLC4A11 supported osmotically driven water accumulation that was electroneutral and Na⁺ independent. Studies in oocytes and HEK293 cells could not detect Na⁺⁻ coupled HCO<sub>3</sub>⁻ transport or Cl⁻/HCO<sub>3</sub>⁻ exchange by SLC4A11. SLC4A11 mediated electroneutral NH3 transport in oocytes. Voltagedependent OH⁻ or H⁺ movement was not measurable in SLC4A11- expressing oocytes, but SLC4A11-expressing HEK293 cells manifested low-level cytosolic acidification at baseline. In mammalian cells, but not oocytes, OH⁻/H⁺ conductance may arise when SLC4A11 activates another protein or itself is activated by another protein. These data argue against a role of human SLC4A11 in bicarbonate or borate transport. This work provides additional support for water and ammonia transport by SLC4A11. When expressed in oocytes, SLC4A11 transported NH<sub>3</sub>, not NH<sub>3</sub>/H⁺.
format Articulo
Articulo
author Loganathan, Sampath K.
Schneider, Hans Peter
Morgan, Patricio Eduardo
Deitmer, Joachim W.
Casey, Joseph R.
author_facet Loganathan, Sampath K.
Schneider, Hans Peter
Morgan, Patricio Eduardo
Deitmer, Joachim W.
Casey, Joseph R.
author_sort Loganathan, Sampath K.
title Functional assessment of SLC4A11, an integral membrane protein mutated in corneal dystrophies
title_short Functional assessment of SLC4A11, an integral membrane protein mutated in corneal dystrophies
title_full Functional assessment of SLC4A11, an integral membrane protein mutated in corneal dystrophies
title_fullStr Functional assessment of SLC4A11, an integral membrane protein mutated in corneal dystrophies
title_full_unstemmed Functional assessment of SLC4A11, an integral membrane protein mutated in corneal dystrophies
title_sort functional assessment of slc4a11, an integral membrane protein mutated in corneal dystrophies
publishDate 2016
url http://sedici.unlp.edu.ar/handle/10915/99458
https://ri.conicet.gov.ar/11336/54183
https://www.physiology.org/doi/10.1152/ajpcell.00078.2016
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5130586/
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