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

Autores
Loganathan, Sampath K.; Schneider, Hans Peter; Morgan, Patricio Eduardo; Deitmer, Joachim W.; Casey, Joseph R.
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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 Xenopus laevis 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 HCO3 - transport or Cl-/HCO3 - 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 NH3, not NH3/H+.
Fil: Loganathan, Sampath K.. University of Alberta; Canadá
Fil: Schneider, Hans Peter. Technische Universtät Kaiserslautern; Alemania
Fil: Morgan, Patricio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Deitmer, Joachim W.. Technische Universtät Kaiserslautern; Alemania
Fil: Casey, Joseph R.. University of Alberta; Canadá
Materia
AMMONIA
CORNEAL DYSTROPHY
ENDOTHELIAL CELL
SLC4A11
WATER FLUX
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/54183
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/54183
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Functional assessment of SLC4A11, an integral membrane protein mutated in corneal dystrophiesLoganathan, Sampath K.Schneider, Hans PeterMorgan, Patricio EduardoDeitmer, Joachim W.Casey, Joseph R.AMMONIACORNEAL DYSTROPHYENDOTHELIAL CELLSLC4A11WATER FLUXhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1SLC4A11, 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 Xenopus laevis 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 HCO3 - transport or Cl-/HCO3 - 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 NH3, not NH3/H+.Fil: Loganathan, Sampath K.. University of Alberta; CanadáFil: Schneider, Hans Peter. Technische Universtät Kaiserslautern; AlemaniaFil: Morgan, Patricio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Deitmer, Joachim W.. Technische Universtät Kaiserslautern; AlemaniaFil: Casey, Joseph R.. University of Alberta; CanadáAmerican Physiological Society2016-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/54183Loganathan, 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; American Physiological Society; American Journal of Physiology-cell Physiology; 311; 5; 8-2016; C735-C7480363-6143CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1152/ajpcell.00078.2016info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/10.1152/ajpcell.00078.2016info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5130586/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:52:11Zoai:ri.conicet.gov.ar:11336/54183instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:52:11.44CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Functional assessment of SLC4A11, an integral membrane protein mutated in corneal dystrophies
title Functional assessment of SLC4A11, an integral membrane protein mutated in corneal dystrophies
spellingShingle Functional assessment of SLC4A11, an integral membrane protein mutated in corneal dystrophies
Loganathan, Sampath K.
AMMONIA
CORNEAL DYSTROPHY
ENDOTHELIAL CELL
SLC4A11
WATER FLUX
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
dc.creator.none.fl_str_mv Loganathan, Sampath K.
Schneider, Hans Peter
Morgan, Patricio Eduardo
Deitmer, Joachim W.
Casey, Joseph R.
author Loganathan, Sampath K.
author_facet Loganathan, Sampath K.
Schneider, Hans Peter
Morgan, Patricio Eduardo
Deitmer, Joachim W.
Casey, Joseph R.
author_role author
author2 Schneider, Hans Peter
Morgan, Patricio Eduardo
Deitmer, Joachim W.
Casey, Joseph R.
author2_role author
author
author
author
dc.subject.none.fl_str_mv AMMONIA
CORNEAL DYSTROPHY
ENDOTHELIAL CELL
SLC4A11
WATER FLUX
topic AMMONIA
CORNEAL DYSTROPHY
ENDOTHELIAL CELL
SLC4A11
WATER FLUX
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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 Xenopus laevis 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 HCO3 - transport or Cl-/HCO3 - 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 NH3, not NH3/H+.
Fil: Loganathan, Sampath K.. University of Alberta; Canadá
Fil: Schneider, Hans Peter. Technische Universtät Kaiserslautern; Alemania
Fil: Morgan, Patricio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Deitmer, Joachim W.. Technische Universtät Kaiserslautern; Alemania
Fil: Casey, Joseph R.. University of Alberta; Canadá
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 Xenopus laevis 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 HCO3 - transport or Cl-/HCO3 - 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 NH3, not NH3/H+.
publishDate 2016
dc.date.none.fl_str_mv 2016-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/54183
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; American Physiological Society; American Journal of Physiology-cell Physiology; 311; 5; 8-2016; C735-C748
0363-6143
CONICET Digital
CONICET
url http://hdl.handle.net/11336/54183
identifier_str_mv 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; American Physiological Society; American Journal of Physiology-cell Physiology; 311; 5; 8-2016; C735-C748
0363-6143
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpcell.00078.2016
info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/10.1152/ajpcell.00078.2016
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5130586/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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