Tropomyosin modulates erythrocyte membrane stability.
The ternary complex of spectrin, actin, and 4.1R (human erythrocyte protein 4.1) defines the nodes of the erythrocyte membrane skeletal network and is inseparable from membrane stability under mechanical stress. These junctions also contain tropomyosin (TM) and the other actin-binding proteins, adducin, protein 4.9, tropomodulin, and a small proportion of capZ, the functions of which are poorly defined. Here, we have examined the consequences of selective elimination of TM from the membrane. We have shown that the mechanical stability of the membranes of resealed ghosts devoid of TM is grossly, but reversibly, impaired. That the decreased membrane stability of TM-depleted membranes is the result of destabilization of the ternary complex of the network junctions is demonstrated by the strongly facilitated entry into the junctions in situ of a beta-spectrin peptide, containing the actin- and 4.1R-binding sites, after extraction of the TM. The stabilizing effect of TM is highly specific, in that it is only the endogenous isotype, and not the slightly longer muscle TM that can bind to the depleted membranes and restore their mechanical stability. These findings have enabled us identify a function for TM in elevating the mechanical stability of erythrocyte membranes by stabilizing the spectrin-actin-4.1R junctional complex.
An
Xiuli
X
Red Cell Physiology Laboratory, New York Blood Center, New York, NY 10021, USA. xan@nybloodcenter.org
Salomao
Marcela
M
Guo
Xinhua
X
Gratzer
Walter
W
Mohandas
Narla
N
D000199:Actins / Q000378:metabolism; D001665:Binding Sites; D001696:Biomechanical Phenomena; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000648:ultrastructure*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D013049:Spectrin / Q000378:metabolism; D014335:Tropomyosin / Q000172:deficiency / Q000502:physiology*
D000199:Actins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D014335:Tropomyosin; C028841:erythrocyte membrane band 4.1 protein; D013049:Spectrin