Phosphatidylserine flipping by the P4-ATPase ATP8A2 is electrogenic

Proceedings of the National Academy of Sciences of the United States of America
Francesco Tadini-BuoninsegniJens Peter Andersen

Abstract

Phospholipid flippases (P4-ATPases) utilize ATP to translocate specific phospholipids from the exoplasmic leaflet to the cytoplasmic leaflet of biological membranes, thus generating and maintaining transmembrane lipid asymmetry essential for a variety of cellular processes. P4-ATPases belong to the P-type ATPase protein family, which also encompasses the ion transporting P2-ATPases: Ca2+-ATPase, Na+,K+-ATPase, and H+,K+-ATPase. In comparison with the P2-ATPases, understanding of P4-ATPases is still very limited. The electrogenicity of P4-ATPases has not been explored, and it is not known whether lipid transfer between membrane bilayer leaflets can lead to displacement of charge across the membrane. A related question is whether P4-ATPases countertransport ions or other substrates in the opposite direction, similar to the P2-ATPases. Using an electrophysiological method based on solid supported membranes, we observed the generation of a transient electrical current by the mammalian P4-ATPase ATP8A2 in the presence of ATP and the negatively charged lipid substrate phosphatidylserine, whereas only a diminutive current was generated with the lipid substrate phosphatidylethanolamine, which carries no or little charge under the condi...Continue Reading

References

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Citations

Sep 17, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Francesco Tadini-Buoninsegni
Mar 29, 2020·Sensors·Francesco Tadini-Buoninsegni, Ilaria Palchetti
Dec 19, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xiaominting SongJin Pei
Jun 4, 2020·Current Opinion in Structural Biology·Joseph A LyonsPoul Nissen
Apr 7, 2021·Plant Physiology·Rosa L López-MarquésMichael Palmgren
May 24, 2021·Journal of Molecular Biology·Milena TimcenkoPoul Nissen

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