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αI-spectrin represents evolutionary optimization of spectrin for red blood cell deformability

Hale, John, An, Xiuli, Guo, Xinhua, Gao, Erjing, Papoin, Julien, Blanc, Lionel, Hillyer, Christopher D., Gratzer, Walter, Baines, Anthony, Mohandas, Narla and others. (2021) αI-spectrin represents evolutionary optimization of spectrin for red blood cell deformability. Biophysical Journal, . ISSN 0006-3495. E-ISSN 1542-0086. (doi:10.1016/j.bpj.2021.07.027) (KAR id:89641)

Abstract

Spectrin tetramers of the membranes of enucleated mammalian erythrocytes play a critical role in red blood cell survival in circulation. One of the spectrins, αI, emerged in mammals with enucleated red cells following duplication of the ancestral α-spectrin gene common to all animals. The neofunctionalized αIspectrin has moderate affinity for βI-spectrin, while αII-spectrin, expressed in non-erythroid cells, retains ancestral characteristics and has a 10-fold higher affinity for βI-spectrin. It has been hypothesized that this adaptation allows for rapid make-and-break of tetramers to accommodate membrane deformation. We

have tested this hypothesis by generating mice with high-affinity spectrin tetramers formed by exchanging the site of tetramer formation in αI-spectrin (segments R0 and R1) for that of αII-spectrin. Erythrocytes with αIIβI presented normal hematologic parameters yet showed increased thermostability and their membranes were significantly less deformable: under low shear forces they displayed tumbling behavior, rather than tank-treading. The membrane skeleton is more stable with αIIβI and shows significantly less remodeling under deformation than red cell membranes of wild-type mice. These data demonstrate that spectrin tetramers undergo remodeling in intact erythrocytes and that this is required for the normal deformability of the erythrocyte membrane. We conclude that αI-spectrin represents evolutionary optimization of tetramer formation: neither higher affinity tetramers (as shown here) nor lower affinity (as seen in hemolytic disease), can support the membrane properties required for effective tissue oxygenation in circulation.

Item Type: Article
DOI/Identification number: 10.1016/j.bpj.2021.07.027
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Susan Grimer
Date Deposited: 05 Aug 2021 16:03 UTC
Last Modified: 14 Nov 2022 23:13 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/89641 (The current URI for this page, for reference purposes)

University of Kent Author Information

Baines, Anthony.

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