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The role of the lipid bilayer on the inhibition of the Plasma membranecalcium ATPase (PMCA) by aluminium Marilina de Sautu, María BelénBianco, Mariela S Ferreira-Gomes, Juan Pablo Rossi and Irene C MangialavoriInstituto de Química yFisicoquímica Biológicas. ?Prof.Paladini?. Departamento de Química Biológica,Facultad de Farmacia y Bioquímica. Universidadde Buenos Aires.Argentina.Email:desautu.marilina@gmail.com PMCA is a P-ATPase involved in the regulation of the cell calciumhomeostasis transporting Ca2+ from cytoplasm towards theextracellular medium. PMCA like other integral membrane proteins operatessurrounded by a complex and dynamic lipid bilayer, and its activity largelydepends on the type of lipids [1]. Aluminium (Al3+ and othersoluble species) is environmentally ubiquitous, providing humanexposure and neurotoxic effects in humans and animals. The mechanisms proposed to explain aluminium toxicity are linked tochanges in the cellular calcium homeostasis. In previous works, we showed that AlCl3 inhibits calciumefflux mediated by PMCA in HEK293T cells. Also, we demonstrated that aluminium inhibits PMCA activity irreversibly bypreventing the dephosphorylation of the pump [1]. The aim of this work is to understand the effect of aluminium on the lipidic environment of PMCA. Aluminiumwould have distinct effect depending on the lipid composition of the cellmembrane where the PMCA is located. To characterize this effect, mixed micellesof phospholipids and detergent (C12E10) were formed at differentmolar fractions and we measured how PMCA activity varied with or without thepresence of aluminium. Further, we characterize theinteraction of aluminium in the same micelles with an aluminum-specific fluorescentprobe (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 interactswith the micelles, in agreement with lumogallion fluorescence changes. [1]Pignataro, M. F et al (2015) Modulation of plasma membrane Ca2+-ATPaseby neutral phospholipids: effect of the micelle-vesicle transition and thebilayer thickness. The Journal of biological chemistry, 290(10), 6179?6190.doi:10.1074/jbc.M114. [2] DeSautu M et al. BBA-Biomembrane (2018) 860(8):1580-1588. doi:10.1016/j.bbamem.2018.05.014 Acknowledgement: This work was supported by ANPCYT PICT 2017- 2615,CONICET PIP 0250 and Universidad de Buenos Aires: 20020130100254B.

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