REGULATION OF Na+,K+-ATPase BY DETYROSINATED TUBULIN. IMPLICANCE IN HYPERTENSIVE SUBJECTS

AMAIDEN MR; MONESTEROLO NE; CASALE CH; SANTANDER VS

Mendoza

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2012

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

Balance between tyrosinated and detyrosinated tubulin is essential for the normal development of thecells. Previously we demonstrated that detyrosinated tubulin is increased in erythrocytes membranes ofhypertensive subjects. Moreover, there is known that in erythrocytes of hypertensive subjects the Na+,K+-ATPase (NKA) activity is decreased in a 50% and that the activity of this enzyme is inhibited by theformation of a complex between the NKA and tubulin. Although it is known that acetylation of tubulin isessential to form the complex has not be studied if another postraslational modifications of tubulin areinvolved in the above mentioned regulatory mechanism. In this work we demonstrate that detyrosinatedtubulin enhanced the inhibition of acetylated tubulin on the NKA activity and changes in levels of detyrosinatedtubulin in the membrane produces modifications on the NKA activity. On the other hand, we show thatthe increase of detyrosinated tubulin in erythrocytes of hypertensive subjects would be a consequence ofa decrease in the content and the activity of the enzyme tubulin tyrosine ligase but not tubulin tyrosinecarboxipeptidase. In conclusion, detyrosination/tyrosination of tubulin has an important role in the regulationof the NKA activity, and then abnormalities in its cycle would be involved in the progression of differentpathologies were NKA is implicated.