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Rh-RhAG/ankyrin-R, a new interaction site between the membrane bilayer and the red cell skeleton, is impaired by Rh(null)-associated mutation.

Several studies suggest that the Rh complex represents a major interaction site between the membrane lipid bilayer and the red cell skeleton, but little is known about the molecular basis of this interaction. We report here that ankyrin-R is capable of interacting directly with the C-terminal cytoplasmic domain of Rh and RhAG polypeptides. We first show that the primary defect of ankyrin-R in normoblastosis (nb/nb) spherocytosis mutant mice is associated with a sharp reduction of RhAG and Rh polypeptides. Secondly, our flow cytometric analysis of the Triton X-100 extractability of recombinant fusion proteins expressed in erythroleukemic cell lines suggests that the C-terminal cytoplasmic domains of Rh and RhAG are sufficient to mediate interaction with the erythroid membrane skeleton. Using the yeast two-hybrid system, we demonstrate a direct interaction between the cytoplasmic tails of Rh and RhAG and the second repeat domain (D2) of ankyrin-R. This finding is supported by the demonstration that the substitution of Asp-399 in the cytoplasmic tail of RhAG, a mutation associated with the deficiency of the Rh complex in one Rhnull patient, totally impaired interaction with domain D2 of ankyrin-R. These results identify the Rh/RhAG-ankyrin complex as a new interaction site between the red cell membrane and the spectrin-based skeleton, the disruption of which might result in the stomato-spherocytosis typical of Rhnull red cells.

Pubmed ID: 12719424


  • Nicolas V
  • Le Van Kim C
  • Gane P
  • Birkenmeier C
  • Cartron JP
  • Colin Y
  • Mouro-Chanteloup I


The Journal of biological chemistry

Publication Data

July 11, 2003

Associated Grants


Mesh Terms

  • Animals
  • Ankyrins
  • Blood Proteins
  • Blotting, Western
  • Calmodulin-Binding Proteins
  • Cytoplasm
  • Detergents
  • Electrophoresis, Polyacrylamide Gel
  • Erythrocytes
  • Flow Cytometry
  • Glutathione Transferase
  • Humans
  • K562 Cells
  • Lipid Bilayers
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred BALB C
  • Mice, Mutant Strains
  • Models, Biological
  • Octoxynol
  • Protein Binding
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins
  • Rh-Hr Blood-Group System
  • Transfection
  • Two-Hybrid System Techniques