Inhibition of flippase-like activity by tubulin regulates phosphatidylserine exposure in erythrocytes from hypertensive and diabetic patients

MUHLBERGER T; BALACH, MM; BISIG, CG,; SANTANDER, VS; MONESTEROLO, N E; CASALE, CH; CAMPETELLI, AN

JOURNAL OF BIOCHEMISTRY

OXFORD UNIV PRESS

Año: 2021

0021-924X

lasma membrane tubulin is an endogenous regulator of P-ATPases and the unusual accumulation of tubulin in the erythrocyte membrane results in a partial inhibition of some their activities, causing hemorheological disorders like reduced cell deformability and osmotic resistance. These disorders are of particular interest in hypertension and diabetes, where the abnormal increase in membrane tubulin may be related to the disease development. Phosphatidylserine (PS) is more exposed on the membrane of diabetic erythrocytes than in healthy cells. In most cells, PS is transported from the exoplasmic to the cytoplasmic leaflet of the membrane by lipid flippases. Here, we report that PS is more exposed in erythrocytes from both hypertensive and diabetic patients than in healthy erythrocytes, which could be attributed to the inhibition of flippase activity by tubulin. This is supported by: (i) the translocation rate of a fluorescent PS analog in hypertensive and diabetic erythrocytes was slower