Molecular and functional characterization of SLC26A11, a sodium-independent sulfate transporter from high endothelial venules.
Lymphocyte emigration from the blood into most secondary lymphoid organs and chronically inflamed tissues occurs at the level of high endothelial venules (HEV). A unique characteristic of HEV endothelial cells (HEVEC) is their capacity to incorporate large amounts of sulfate into sialomucin-type counter-receptors for the lymphocyte homing receptor L-selectin. We have previously shown that sulfate uptake into HEVEC is mediated by two distinct functional classes of sulfate transporters: Na+-coupled transporters and sulfate/anion exchangers. Here, we report the molecular characterization from human HEVEC of SLC26A11, a novel member of the SLC26 sulfate/anion exchanger family. Functional expression studies in COS-7 and Sf9 insect cells revealed that SLC26A11 is targeted to the cell membrane and exhibits Na+-independent sulfate transport activity, sensitive to the anion exchanger inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Northern blot analysis showed the highest SLC26A11 transcript levels in placenta, kidney, and brain. The SLC26A11 gene mapped to human chromosome 17q25, very close to the hereditary hearing loss diseases loci DFNA20, DFNA26, and USH1G. RT-PCR analysis of SLC26 sulfate transporters in human HEVEC revealed coexpression of SLC26A11 with SLC26A2/DTDST and lack of SLC26A1/SAT1, SLC26A3/DRA, and SLC26A8/TAT1. Together, our results indicate that SLC26A11 is a novel Na+-independent sulfate transporter that may cooperate with SLC26A2 to mediate DIDS-sensitive sulfate uptake into HEVEC.
Vincourt
Jean-Baptiste
JB
Laboratoire de Biologie Vasculaire, Institut de Pharmacologie et de Biologie Structurale du CNRS, Toulouse, France.
Jullien
Denis
D
Amalric
Francois
F
Girard
Jean-Philippe
JP
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics* / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression; D020022:Genetic Predisposition to Disease / Q000235:genetics; D034381:Hearing Loss / Q000235:genetics; D006801:Humans; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D012964:Sodium / Q000494:pharmacology; D018411:Spodoptera; D000076988:Sulfate Transporters
D027321:Anion Transport Proteins; D002352:Carrier Proteins; D018076:DNA, Complementary; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C089651:SLC26A2 protein, human; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D012964:Sodium; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid