Publication: C3b deposition on human erythrocytes induces the formation of a membrane skeleton-linked protein complex
Issued Date
2009-04-01
Resource Type
ISSN
15588238
00219738
00219738
DOI
Other identifier(s)
2-s2.0-65249110965
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Clinical Investigation. Vol.119, No.4 (2009), 788-801
Suggested Citation
Pallop Karnchanaphanurach, Rossen Mirchev, Ionita Ghiran, John M. Asara, Brigitte Papahadjopoulos-Sternberg, Anne Nicholson-Weller, David E. Golan C3b deposition on human erythrocytes induces the formation of a membrane skeleton-linked protein complex. Journal of Clinical Investigation. Vol.119, No.4 (2009), 788-801. doi:10.1172/JCI36088 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/28133
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
C3b deposition on human erythrocytes induces the formation of a membrane skeleton-linked protein complex
Abstract
Decay-accelerating factor (DAF, also known as CD55), a glycosylphosphatidylinositol-linked (GPI-linked) plasma membrane protein, protects autologous cells from complement-mediated damage by inhibiting complement component 3 (C3) activation. An important physical property of GPI-anchored complement regulatory proteins such as DAF is their ability to translate laterally in the plasma membrane. Here, we used singleparticle tracking and tether-pulling experiments to measure DAF lateral diffusion, lateral confinement, and membrane skeletal associations in human erythrocyte membranes. In native membranes, most DAF molecules exhibited Brownian lateral diffusion. Fluid-phase complement activation caused deposition of C3b, one of the products of C3 cleavage, onto erythrocyte glycophorin A (GPA). We then determined that DAF, C3b, GPA, and band 3 molecules were laterally immobilized in the membranes of complement-treated cells, and GPA was physically associated with the membrane skeleton. Mass spectrometry analysis further showed that band 3, α-spectrin, β-spectrin, and ankyrin were present in a complex with C3b and GPA in complement-treated cells. C3b deposition was also associated with a substantial increase in erythrocyte membrane stiffness and/or viscosity. We therefore suggest that complement activation stimulates the formation of a membrane skeleton-linked DAF-C3b-GPA-band 3 complex on the erythrocyte surface. This complex may promote the removal of senescent erythrocytes from the circulation.