Tubulin-mediated anatomical and functional changes caused by Ca 2+ in human erythrocytes

In previous research, we observed that tubulin can be found in three fractions within erythrocytes, i.e., attached to the membrane, as a soluble fraction, or as part of a structure that can be sedimented by centrifugation. Given that its differential distribution within these fractions may alter several hemorheological properties, such as erythrocyte deformability, the present work studied how this distribution is in turn affected by Ca 2+ , another key player in the regulation of erythrocyte cytoskeleton stability. The effect of Ca 2+ on some hemorheological parameters was also assessed. The results showed that when Ca 2+ concentrations increased in the cell, whether by the addition of ionophore A23187, by specific plasma membrane Ca 2 + _ ATPase (PMCA) inhibition, or due to arterial hypertension, tubulin translocate to the membrane, erythrocyte deformability decreased, and phosphatidylserine exposure increased. Moreover, increased Ca 2+ was associated with an inverse correlation in the distribution of tubulin and spectrin, another important cytoskeleton protein. Based on these findings, we propose the existence of a mechanism of action through which higher Ca 2+ concentrations in erythrocytes trigger the migration of tubulin to the membrane, a phenomenon that results in alterations of rheological and molecular aspects of the membrane itself, as well as of the integrity of the cytoskeleton. Graphical Abstract