Haematologica, Vol 94, Issue 10, 1354-1361 doi:10.3324/haematol.2009.006585
Copyright © 2009 by Ferrata Storti Foundation
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Red Cell Disorders

4.1R-deficient human red blood cells have altered phosphatidylserine exposure pathways and are deficient in CD44 and CD47 glycoproteins

Kris P. Jeremy1, Zoe E. Plummer1, David J. Head1, Tracey E. Madgett1, Kelly L. Sanders1, Amanda Wallington1, Jill R. Storry2, Florinda Gilsanz3, Jean Delaunay4, Neil D. Avent5

1 University of the West of England, Bristol, UK
2 Blood Centre, University Hospital, Lund, Sweden
3 Hematologia, Hospital '12 de Octubre’ "Instituto National de la Salud", Carretera de Andalucia, Madrid, Spain
4 INSERM U 779, Faculté de Médecine Paris-Sud, Univ Paris-Sud, Le Kremlin-Bicêtre, France
5 School of Biomedical and Biological Sciences, University of Plymouth, UK

Correspondence: Neil D. Avent, School of Biomedical and Biological Sciences, University of Plymouth, Drake Circus, Plymouth, PL4 8AA, UK E-mail:neil.avent{at}plymouth.ac.uk

Background: Protein 4.1R is an important component of the red cell membrane skeleton. It imparts structural integrity and has transmembrane signaling roles by direct interactions with transmembrane proteins and other membrane skeletal components, notably p55 and calmodulin.

Design and Methods: Spontaneous and ligation-induced phosphatidylserine exposure on erythrocytes from two patients with 4.1R deficiency were studied, using CD47 glycoprotein and glycophorin C as ligands. We also looked for protein abnormalities in the 4.1R - based multiprotein complex.

Results: Phosphatidylserine exposure was significantly increased in 4.1R-deficient erythrocytes obtained from the two different individuals when ligands to CD47 glycoprotein were bound. Spontaneous phosphatidylserine exposure was normal. 4.1R, glycophorin C and p55 were missing or sharply reduced. Furthermore there was an alteration or deficiency of CD47 glycoprotein and a lack of CD44 glycoprotein. Based on a recent study in 4.1R-deficient mice, we found that there are clear functional differences between interactions of human red cell 4.1R and its murine counterpart.

Conclusions: Glycophorin C is known to bind 4.1R, and we have defined previously that it also binds CD47. From our evidence, we suggest that 4.1R plays a role in the phosphatidylserine exposure signaling pathway that is of fundamental importance in red cell turnover. The linkage of CD44 to 4.1R may be relevant to this process.

Key words: phosphatidylserine, 4.1R deficiency, CD44, CD47, glycophorin C.