Complete deficiency of glycophorin A in red blood cells from mice with targeted inactivation of the band 3 (AE1) gene.
Glycophorin A is the major transmembrane sialoglycoprotein of red blood cells. It has been shown to contribute to the expression of the MN and Wright blood group antigens, to act as a receptor for the malaria parasite Plasmodium falciparum and Sendai virus, and along with the anion transporter, band 3, may contribute to the mechanical properties of the red blood cell membrane. Several lines of evidence suggest a close interaction between glycophorin A and band 3 during their biosynthesis. Recently, we have generated mice where the band 3 expression was completely eliminated by selective inactivation of the AE1 anion exchanger gene, thus allowing us to study the effect of band 3 on the expression of red blood cell membrane proteins. In this report, we show that the band 3 -/- red blood cells contain protein 4.1, adducin, dematin, p55, and glycophorin C. In contrast, the band 3 -/- red blood cells are completely devoid of glycophorin A (GPA), as assessed by Western blot and immunocytochemistry techniques, whereas the polymerase chain reaction (PCR) confirmed the presence of GPA mRNA. Pulse-label and pulse-chase experiments show that GPA is not incorporated in the membrane and is rapidly degraded in the cytoplasm. Based on these findings and other published evidence, we propose that band 3 plays a chaperone-like role, which is necessary for the recruitment of GPA to the red blood cell plasma membrane.
Hassoun
H
H
Laboratory of Tumor Cell Biology, Department of Biomedical Research, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA 02135, USA.
Hanada
T
T
Lutchman
M
M
Sahr
K E
KE
Palek
J
J
Hanspal
M
M
Chishti
A H
AH
D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D001692:Biological Transport; D001798:Blood Proteins / Q000032:analysis; D004910:Erythrocyte Membrane / Q000378:metabolism*; D006021:Glycophorins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis
D001457:Anion Exchange Protein 1, Erythrocyte; D001798:Blood Proteins; D006021:Glycophorins; D008565:Membrane Proteins; D012333:RNA, Messenger