The role of the lipid bilayer on the inhibition of the Plasma membrane calcium ATPase (PMCA) by aluminium

DE SAUTU, MARILINA; BIANCO B; FERREIRA GOMES, MARIELA; ROSSI J. P. F. C.; MANGIALAVORI IRENE

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Biofísica; 2019

PMCA is a P-ATPase involved in the regulation of the cell calcium homeostasistransporting Ca2+ from cytoplasm towards the extracellular medium. PMCA like otherintegral membrane proteins operates surrounded by a complex and dynamic lipidbilayer, and its activity largely depends on the type of lipids [1]. Aluminium (Al3+ andother soluble species) is environmentally ubiquitous, providing human exposure andneurotoxic effects in humans and animals. The mechanisms proposed to explainaluminium toxicity are linked to changes in the cellular calcium homeostasis. In previousworks, we showed that AlCl3 inhibits calcium efflux mediated by PMCA in HEK293T cells.Also, we demonstrated that aluminium inhibits PMCA activity irreversibly by preventingthe dephosphorylation of the pump [1].The aim of this work is to understand the effect of aluminium on the lipidic environmentof PMCA. Aluminium would have distinct effect depending on the lipid composition of thecell membrane where the PMCA is located. To characterize this effect, mixed micelles ofphospholipids and detergent (C12E10) were formed at different molar fractions and wemeasured how PMCA activity varied with or without the presence of aluminium. Further,we characterize the interaction of aluminium in the same micelles with an aluminumspecific fluorescent probe (Lumogallion).Our results indicate that the inhibition of the pump by aluminium depends largely on thecomposition and concentration of phospholipids surrounding PMCA. Moreover, we showhow aluminium interacts with the micelles, in agreement with lumogallion fluorescencechanges.References[1] Pignataro, M. F et al (2015). J. Biol. Chem., 290(10), 6179?6190.[2] De Sautu M et al. BBA-Biomembrane (2018) 860(8):1580-1588.AcknowldegmentsThis work was supported by Agencia Nacional de Promoción Científica y Tecnológica (PRESTAMO BIDPICT-2017-2615 and 2015-0067) and Universidad de Buenos Aires (UBACYT- 20020130100254B)