The human Kell blood group binds the erythroid 4.1R protein: new insights into the 4.1R-dependent red cell membrane complex
Slim Azouzi
Institut National de la Transfusion Sanguine, Paris, France
Inserm, UMR_S1134, Paris, France
Université Paris Diderot, Sorbonne Paris Cité, Paris, France
Laboratory of Excellence GR-Ex, New York, NY, USA
These authors contributed equally to this work.Search for more papers by this authorEmmanuel Collec
Institut National de la Transfusion Sanguine, Paris, France
Inserm, UMR_S1134, Paris, France
Université Paris Diderot, Sorbonne Paris Cité, Paris, France
Laboratory of Excellence GR-Ex, New York, NY, USA
These authors contributed equally to this work.Search for more papers by this authorYves Colin
Institut National de la Transfusion Sanguine, Paris, France
Inserm, UMR_S1134, Paris, France
Université Paris Diderot, Sorbonne Paris Cité, Paris, France
Laboratory of Excellence GR-Ex, New York, NY, USA
These authors contributed equally to this work.Search for more papers by this authorCorresponding Author
Caroline Le Van Kim
Institut National de la Transfusion Sanguine, Paris, France
Inserm, UMR_S1134, Paris, France
Université Paris Diderot, Sorbonne Paris Cité, Paris, France
Laboratory of Excellence GR-Ex, New York, NY, USA
These authors contributed equally to this work.Correspondence: Caroline Le Van Kim, UMR_S1134, Institut National de la Transfusion Sanguine, 6 rue Alexandre Cabanel, 75015 Paris, France.
E-mail: [email protected]
Search for more papers by this authorSlim Azouzi
Institut National de la Transfusion Sanguine, Paris, France
Inserm, UMR_S1134, Paris, France
Université Paris Diderot, Sorbonne Paris Cité, Paris, France
Laboratory of Excellence GR-Ex, New York, NY, USA
These authors contributed equally to this work.Search for more papers by this authorEmmanuel Collec
Institut National de la Transfusion Sanguine, Paris, France
Inserm, UMR_S1134, Paris, France
Université Paris Diderot, Sorbonne Paris Cité, Paris, France
Laboratory of Excellence GR-Ex, New York, NY, USA
These authors contributed equally to this work.Search for more papers by this authorYves Colin
Institut National de la Transfusion Sanguine, Paris, France
Inserm, UMR_S1134, Paris, France
Université Paris Diderot, Sorbonne Paris Cité, Paris, France
Laboratory of Excellence GR-Ex, New York, NY, USA
These authors contributed equally to this work.Search for more papers by this authorCorresponding Author
Caroline Le Van Kim
Institut National de la Transfusion Sanguine, Paris, France
Inserm, UMR_S1134, Paris, France
Université Paris Diderot, Sorbonne Paris Cité, Paris, France
Laboratory of Excellence GR-Ex, New York, NY, USA
These authors contributed equally to this work.Correspondence: Caroline Le Van Kim, UMR_S1134, Institut National de la Transfusion Sanguine, 6 rue Alexandre Cabanel, 75015 Paris, France.
E-mail: [email protected]
Search for more papers by this authorSummary
Protein 4.1R plays an important role in maintaining the mechanical properties of the erythrocyte membrane. We analysed the expression of Kell blood group protein in erythrocytes from a patient with hereditary elliptocytosis associated with complete 4.1R deficiency (4.1(−) HE). Flow cytometry and Western blot analyses revealed a severe reduction of Kell. In vitro pull down and co-immunoprecipitation experiments from erythrocyte membranes showed a direct interaction between Kell and 4.1R. Using different recombinant domains of 4.1R and the cytoplasmic domain of Kell, we demonstrated that the R46R motif in the juxta-membrane region of Kell binds to lobe B of the 4.1R FERM domain. We also observed that 4.1R deficiency is associated with a reduction of XK and DARC (also termed ACKR1) proteins, the absence of the glycosylated form of the urea transporter B and a slight decrease of band 3. The functional alteration of the 4.1(−) HE erythrocyte membranes was also determined by measuring various transport activities. We documented a slower rate of HCO3−/Cl− exchange, but normal water and ammonia transport across erythrocyte membrane in the absence of 4.1. These findings provide novel insights into the structural organization of blood group antigen proteins into the 4.1R complex of the human red cell membrane.
References
- van den Akker, E., Satchwell, T.J., Pellegrin, S., Flatt, J.F., Maigre, M., Daniels, G., Delaunay, J., Bruce, L.J. & Toye, A.M. (2010a) Investigating the key membrane protein changes during in vitro erythropoiesis of protein 4.2 (−) cells (mutations Chartres 1 and 2). Haematologica, 95, 1278–1286.
- van den Akker, E., Satchwell, T.J., Williamson, R.C. & Toye, A.M. (2010b) Band 3 multiprotein complexes in the red cell membrane; of mice and men. Blood Cells, Molecules, & Diseases, 45, 1–8.
- An, X.L., Takakuwa, Y., Manno, S., Han, B.G., Gascard, P. & Mohandas, N. (2001) Structural and functional characterization of protein 4.1R-phosphatidylserine interaction: potential role in 4.1R sorting within cells. Journal of Biological Chemistry, 276, 35778–35785.
- Anderson, R.A. & Lovrien, R.E. (1984) Glycophorin is linked by band 4.1 protein to the human erythrocyte membrane skeleton. Nature, 307, 655–658.
- Arashiki, N., Kimata, N., Manno, S., Mohandas, N. & Takakuwa, Y. (2013) Membrane peroxidation and methemoglobin formation are both necessary for band 3 clustering: mechanistic insights into human erythrocyte senescence. Biochemistry, 52, 5760–5769.
- Azouzi, S., Gueroult, M., Ripoche, P., Genetet, S., Colin Aronovicz, Y., Le Van Kim, C., Etchebest, C. & Mouro-Chanteloup, I. (2013) Energetic and molecular water permeation mechanisms of the human red blood cell urea transporter B. PLoS ONE, 8, e82338.
- Bell, A.J., Satchwell, T.J., Heesom, K.J., Hawley, B.R., Kupzig, S., Hazell, M., Mushens, R., Herman, A. & Toye, A.M. (2013) Protein distribution during human erythroblast enucleation in vitro. PLoS ONE, 8, e60300.
- Burton, N.M. & Bruce, L.J. (2011) Modelling the structure of the red cell membrane. Biochemistry and Cell Biology, 89, 200–215.
- Carbonnet, F., Hattab, C., Collec, E., Le van Kim, C., Cartron, J.P. & Bertrand, O. (1997) Immunochemical analysis of the Kx protein from human red cells of different Kell phenotypes using antibodies raised against synthetic peptides. British Journal of Haematology, 96, 857–863.
- Cherif-Zahar, B., Raynal, V., Le Van Kim, C., D'Ambrosio, A.M., Bailly, P., Cartron, J.P. & Colin, Y. (1993) Structure and expression of the RH locus in the Rh-deficiency syndrome. Blood, 82, 656–662.
- Cherif-Zahar, B., Raynal, V., Gane, P., Mattei, M.G., Bailly, P., Gibbs, B., Colin, Y. & Cartron, J.P. (1996) Candidate gene acting as a suppressor of the RH locus in most cases of Rh-deficiency. Nature Genetics, 12, 168–173.
- Conboy, J., Kan, Y.W., Shohet, S.B. & Mohandas, N. (1986) Molecular cloning of protein 4.1, a major structural element of the human erythrocyte membrane skeleton. Proceedings of the National Academy of Sciences of the United States of America, 83, 9512–9516.
- Frumence, E., Genetet, S., Ripoche, P., Iolascon, A., Andolfo, I., Le Van Kim, C., Colin, Y., Mouro-Chanteloup, I. & Lopez, C. (2013) Rapid Cl-/HCOFormula exchange kinetics of AE1 in HEK293 cells and hereditary stomatocytosis red blood cells. American Journal of Physiology. Cell Physiology, 305, C654–C662.
- Gane, P., Le Van Kim, C., Bony, V., El Nemer, W., Mouro, I., Nicolas, V., Colin, Y. & Cartron, J.P. (2001) Flow cytometric analysis of the association between blood group-related proteins and the detergent-insoluble material of K562 cells and erythroid precursors. British Journal of Haematology, 113, 680–688.
- Gauthier, E., Guo, X., Mohandas, N. & An, X. (2011) Phosphorylation-dependent perturbations of the 4.1R-associated multiprotein complex of the erythrocyte membrane. Biochemistry, 50, 4561–4567.
- Genetet, S., Ripoche, P., Picot, J., Bigot, S., Delaunay, J., Armari-Alla, C., Colin, Y. & Mouro-Chanteloup, I. (2012) Human RhAG ammonia channel is impaired by the Phe65Ser mutation in overhydrated stomatocytic red cells. American Journal of Physiology. Cell Physiology, 302, C419–C428.
- Hayette, S., Dhermy, D., dos Santos, M.E., Bozon, M., Drenckhahn, D., Alloisio, N., Texier, P., Delaunay, J. & Morle, L. (1995) A deletional frameshift mutation in protein 4.2 gene (allele 4.2 Lisboa) associated with hereditary hemolytic anemia. Blood, 85, 250–256.
- Hermand, P., Mouro, I., Huet, M., Bloy, C., Suyama, K., Goldstein, J., Cartron, J.P. & Bailly, P. (1993) Immunochemical characterization of rhesus proteins with antibodies raised against synthetic peptides. Blood, 82, 669–676.
- Jaber, A., Loirat, M.J., Willem, C., Bloy, C., Cartron, J.P. & Blanchard, D. (1991) Characterization of murine monoclonal antibodies directed against the Kell blood group glycoprotein. British Journal of Haematology, 79, 311–315.
- Jeremy, K.P., Plummer, Z.E., Head, D.J., Madgett, T.E., Sanders, K.L., Wallington, A., Storry, J.R., Gilsanz, F., Delaunay, J. & Avent, N.D. (2009) 4.1R-deficient human red blood cells have altered phosphatidylserine exposure pathways and are deficient in CD44 and CD47 glycoproteins. Haematologica, 94, 1354–1361.
- Ji, Y., Veldhuisen, B., Ligthart, P., Haer-Wigman, L., Jongerius, J., Boujnan, M., Ait Soussan, A., Luo, G., Fu, Y., van der Schoot, C.E. & de Haas, M. (2015) Novel alleles at the Kell blood group locus that lead to Kell variant phenotype in the Dutch population. Transfusion, 55, 413–421.
- Jons, T. & Drenckhahn, D. (1992) Identification of the binding interface involved in linkage of cytoskeletal protein 4.1 to the erythrocyte anion exchanger. EMBO Journal, 11, 2863–2867.
- Khamlichi, S., Bailly, P., Blanchard, D., Goossens, D., Cartron, J.P. & Bertrand, O. (1995) Purification and partial characterization of the erythrocyte Kx protein deficient in McLeod patients. European Journal of Biochemistry, 228, 931–934.
- Kodippili, G.C., Spector, J., Sullivan, C., Kuypers, F.A., Labotka, R., Gallagher, P.G., Ritchie, K. & Low, P.S. (2009) Imaging of the diffusion of single band 3 molecules on normal and mutant erythrocytes. Blood, 113, 6237–6245.
- Kroviarski, Y., El Nemer, W., Gane, P., Rahuel, C., Gauthier, E., Lecomte, M.C., Cartron, J.P., Colin, Y. & Le Van Kim, C. (2004) Direct interaction between the Lu/B-CAM adhesion glycoproteins and erythroid spectrin. British Journal of Haematology, 126, 255–264.
- Lee, S., Russo, D.C., Reiner, A.P., Lee, J.H., Sy, M.Y., Telen, M.J., Judd, W.J., Simon, P., Rodrigues, M.J., Chabert, T., Poole, J., Jovanovic-Srzentic, S., Levene, C., Yahalom, V. & Redman, C.M. (2001) Molecular defects underlying the Kell null phenotype. Journal of Biological Chemistry, 276, 27281–27289.
- Lee, S., Debnath, A.K. & Redman, C.M. (2003) Active amino acids of the Kell blood group protein and model of the ectodomain based on the structure of neutral endopeptidase 24.11. Blood, 102, 3028–3034.
- Liu, J., Guo, X., Mohandas, N., Chasis, J.A. & An, X. (2010) Membrane remodeling during reticulocyte maturation. Blood, 115, 2021–2027.
- Montel-Hagen, A., Blanc, L., Boyer-Clavel, M., Jacquet, C., Vidal, M., Sitbon, M. & Taylor, N. (2008) The Glut1 and Glut4 glucose transporters are differentially expressed during perinatal and postnatal erythropoiesis. Blood, 112, 4729–4738.
- Mouro-Chanteloup, I., D'Ambrosio, A.M., Gane, P., Le Van Kim, C., Raynal, V., Dhermy, D., Cartron, J.P. & Colin, Y. (2002) Cell-surface expression of RhD blood group polypeptide is posttranscriptionally regulated by the RhAG glycoprotein. Blood, 100, 1038–1047.
- Mouro-Chanteloup, I., Delaunay, J., Gane, P., Nicolas, V., Johansen, M., Brown, E.J., Peters, L.L., Van Kim, C.L., Cartron, J.P. & Colin, Y. (2003) Evidence that the red cell skeleton protein 4.2 interacts with the Rh membrane complex member CD47. Blood, 101, 338–344.
- Nunomura, W. & Takakuwa, Y. (2006) Regulation of protein 4.1R interactions with membrane proteins by Ca2+ and calmodulin. Frontiers in Bioscience, 11, 1522–1539.
- Nunomura, W., Denker, S.P., Barber, D.L., Takakuwa, Y. & Gascard, P. (2012) Characterization of cytoskeletal protein 4.1R interaction with NHE1 (Na(+)/H(+) exchanger isoform 1). The Biochemical Journal, 446, 427–435.
- Olives, B., Mattei, M.G., Huet, M., Neau, P., Martial, S., Cartron, J.P. & Bailly, P. (1995) Kidd blood group and urea transport function of human erythrocytes are carried by the same protein. Journal of Biological Chemistry, 270, 15607–15610.
- el Ouggouti, S., Bournier, O., Boivin, P., Bertrand, O. & Dhermy, D. (1992) Purification of erythrocyte protein 4.1 by selective interaction with inositol hexaphosphate. Protein Expression and Purification, 3, 488–496.
- Redman, C.M., Russo, D. & Lee, S. (1999) Kell, Kx and the McLeod syndrome. Baillière's Best Practice and Research. Clinical Haematology, 12, 621–635.
- Ripoche, P., Bertrand, O., Gane, P., Birkenmeier, C., Colin, Y. & Cartron, J.P. (2004) Human Rhesus-associated glycoprotein mediates facilitated transport of NH(3) into red blood cells. Proceedings of the National Academy of Sciences of the United States of America, 101, 17222–17227.
- Rivera, A., De Franceschi, L., Peters, L.L., Gascard, P., Mohandas, N. & Brugnara, C. (2006) Effect of complete protein 4.1R deficiency on ion transport properties of murine erythrocytes. American Journal of Physiology. Cell Physiology, 291, C880–C886.
- Rivera, A., Kam, S.Y., Ho, M., Romero, J.R. & Lee, S. (2013) Ablation of the Kell/Xk complex alters erythrocyte divalent cation homeostasis. Blood Cells, Molecules, & Diseases, 50, 80–85.
- Russo, D., Redman, C. & Lee, S. (1998) Association of XK and Kell blood group proteins. Journal of Biological Chemistry, 273, 13950–13956.
- Salomao, M., Zhang, X., Yang, Y., Lee, S., Hartwig, J.H., Chasis, J.A., Mohandas, N. & An, X. (2008) Protein 4.1R-dependent multiprotein complex: new insights into the structural organization of the red blood cell membrane. Proceedings of the National Academy of Sciences of the United States of America, 105, 8026–8031.
- Salomao, M., Chen, K., Villalobos, J., Mohandas, N., An, X. & Chasis, J.A. (2010) Hereditary spherocytosis and hereditary elliptocytosis: aberrant protein sorting during erythroblast enucleation. Blood, 116, 267–269.
- Satchwell, T.J., Bell, A.J., Pellegrin, S., Kupzig, S., Ridgwell, K., Daniels, G., Anstee, D.J., van den Akker, E. & Toye, A.M. (2011) Critical band 3 multiprotein complex interactions establish early during human erythropoiesis. Blood, 118, 182–191.
- Takakuwa, Y. (2000) Protein 4.1, a multifunctional protein of the erythrocyte membrane skeleton: structure and functions in erythrocytes and nonerythroid cells. International Journal of Hematology, 72, 298–309.
- Takakuwa, Y., Tchernia, G., Rossi, M., Benabadji, M. & Mohandas, N. (1986) Restoration of normal membrane stability to unstable protein 4.1-deficient erythrocyte membranes by incorporation of purified protein 4.1. The Journal of Clinical Investigation, 78, 80–85.
- Tchernia, G., Mohandas, N. & Shohet, S.B. (1981) Deficiency of skeletal membrane protein band 4.1 in homozygous hereditary elliptocytosis. Implications for erythrocyte membrane stability. The Journal of Clinical Investigation, 68, 454–460.
- Trinh-Trang-Tan, M.M., Lasbennes, F., Gane, P., Roudier, N., Ripoche, P., Cartron, J.P. & Bailly, P. (2002) UT-B1 proteins in rat: tissue distribution and regulation by antidiuretic hormone in kidney. American Journal of Physiology. Renal Physiology, 283, F912–F922.
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