Anion exchangers in flux: functional differences between human and mouse SLC26A6 polypeptides.
Novartis Found Symp
; 273: 107-19; discussion 119-25, 261-4, 2006.
Article
en En
| MEDLINE
| ID: mdl-17120764
ABSTRACT
The SLC26 anion transporter polypeptides exhibit considerably greater sequence diversity among near-species orthologues than is found among the SLC4 bicarbonate transporters, and among SLC26 transporters is most marked among SLC26A6 orthologues. This observation prompted systematic functional comparison in Xenopus oocytes of mouse Slc26a6 with several human SLC26A6 polypeptide variants. Mouse and human polypeptides exhibited similar rates of bidirectional [14C]oxalate flux, Cl-/HCO3- exchange, and Cl-/OH- exchange, and similar cAMP-stimulation and enhancement of that stimulation by wild-type but not delta F508 CFTR. However, high rates of 36Cl- and 35S-sulfate transport by mouse Slc26a6 contrasted with low transport rates of the human proteins. The high 36Cl- transport phenotype cosegregated with the transmembrane domain of mouse Slc26a6 in chimera studies. Mouse Slc26a6 and human SLC26A6 each mediated electroneutral Cl-/HCO3- and Cl-/OH- exchange. But, whereas Cl-/oxalate exchange by mouse Slc26a6 was electrogenic, that mediated by human SLC26A6 appeared electroneutral. Oocyte expression of either mouse or human orthologue elicited currents that were pharmacologically distinct from the monovalent anion exchange activities measured in the same lots of oocytes. The human SLC26A6 polypeptide variants SLC26A6c and SLC26A6d were inactive in isotopic flux assays. Understanding of SLC26 transport mechanisms and pathophysiology will benefit from recognition of substantial differences in transport properties among orthologues.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Péptidos
/
Proteínas de Transporte de Membrana
/
Antiportadores
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Novartis Found Symp
Asunto de la revista:
MEDICINA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos