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Urea transport and Kidd blood groups
1INSERM U76, Institut National de la Transfusion Sanguine, Paris.
Insights
The Kidd blood group gene locus encodes the human erythrocyte urea transporter (HUT11). This discovery links the Kidd protein to urea transport defects in Jk(a-b-) individuals, impacting red blood cell function.
Area of Science:
- Molecular Biology
- Genetics
- Physiology
Background:
- The human erythrocyte urea transporter (HUT11) gene was recently cloned.
- The HUT11 gene is localized to chromosome 18q12-q21, similar to the Kidd blood group gene.
- Individuals with the Jk(a-b-) phenotype exhibit a selective defect in urea transport.
Purpose of the Study:
- To investigate the molecular identity of the human erythrocyte urea transporter.
- To determine if the Kidd blood group locus is associated with urea transport in red blood cells.
Main Methods:
- In vitro translation of HUT11 cDNA.
- Immunoprecipitation using anti-Jk3 antibody.
- Western blot analysis with an anti-HUT11 N-terminal antibody.
- N-glycanase digestion of erythrocyte proteins.
Main Results:
- HUT11 cDNA directed the synthesis of a 36 kDa protein immunoprecipitated by anti-Jk3 antibody.
- Anti-Jk3 and anti-HUT11 antibodies detected a 46-60 kDa glycoprotein in red blood cells, absent in Jk(a-b-) individuals.
- N-glycanase digestion reduced the glycoprotein size to 36 kDa, consistent with the in vitro translation product.
- Jk(a-b-) red blood cells lack both Kidd protein and HUT11 urea transporter, showing normal water transport and aquaporin-1 expression.
Conclusions:
- The Kidd locus encodes the human erythrocyte urea transporter (HUT11).
- This finding establishes a direct link between the Kidd blood group and urea transport function.
- Opens new avenues for studying urea transporter biology and tissue-specific regulation.
Abstract:
The gene encoding for the human erythrocyte urea transporter (HUT11 clone) has recently been cloned (Olives et al., J. Biol. Chem., 269, 3/649, 1994). It has been localized at 18q12-q21, like the Kidd blood group gene. In vitro translation experiments indicated that cDNA HUT11 could induce the synthesis of a 36 kDa protein which can be immunoprecipitated by an anti-Jk3 antibody (a human antibody produced by Jk(a-b-) individuals). This antibody also precipitates a 46-60 kDa protein from human red blood cells, except from those with Jk(a-b-) phenotype. After N-glycanase digestion, the length of the glycoprotein was reduced from 46-60 kDa to 36 kDa. Moreover, a rabbit antibody directed against the N-terminal end of HUT11 protein reacts in western-blot with 46-60 kDa proteins present in all human red blood cells, except those with Jk(a-b-) phenotype. Jk(a-b-) cells have neither Kidd protein nor HUT11 urea transporter and they are characterized by a selective defect of urea transport whereas water transport and aquaporin-1 associated Colton antigens are normally expressed. All these findings provide evidence that the Kidd locus encodes for the human erythrocyte urea transporter, offering new prospects for biological study of urea transporters and their tissue-specific regulation.