Alteration of alpha-spectrin ubiquitination due to age-dependent changes in the erythrocyte membrane.
Mammalian red blood cell alpha-spectrin is ubiquitinated in vitro and in vivo [Corsi, D., Galluzzi, L., Crinelli, R., Magnani, M. (1995) J. Biol. Chem. 270, 8928-8935]. This process shows a cell age-dependent decrease, with senescent red blood cells having approximately one third of the amount of ubiquitinated alpha-spectrin found in young cells. In-vitro ubiquitination of alpha-spectrin was dependent on the source of the red cell membranes (those from older cells are less susceptible to ubiquitination than those from younger cells), on the source of ubiquitin-conjugating enzymes (those from older cells catalyze the process at a reduced rate compared to those from younger cells) and on the ubiquitin isopeptidase activity (which decreases during red cell ageing). However, once alpha-spectrin has been extracted from the membranes of young or old red blood cells, it is susceptible to ubiquitination to a similar extent regardless of source. This suggests that it is the membrane architecture, and not spectrin itself, that is responsible for the age-dependent decline in ubiquitination. Furthermore, spectrin oligomers, tetramers and dimers are also equally susceptible to ubiquitination. As spectrin ubiquitination occurs on domains alphaIII and alphaV of alpha-spectrin, and domain alphaV contains the nucleation site for the association of the alpha- and beta-spectrin chains, alterations in ubiquitination during red cell ageing could affect the stability and deformability of the erythrocyte membrane.
Corsi
D
D
G. Fornaini Institute of Biological Chemistry, University of Urbino, Italy.
Paiardini
M
M
Crinelli
R
R
Bucchini
A
A
Magnani
M
M
D016922:Cellular Senescence; D019281:Dimerization; D010450:Endopeptidases / Q000097:blood; D004910:Erythrocyte Membrane / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D013049:Spectrin / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*
D014452:Ubiquitins; D013049:Spectrin; D010450:Endopeptidases; C091939:ubiquitin isopeptidase