Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Department of Cell Biology, Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
EMBO J. 2018 May 2;37(9). doi: 10.15252/embj.201797705. Epub 2018 Mar 29.
P4-ATPases are phospholipid flippases that translocate phospholipids from the exoplasmic/luminal to the cytoplasmic leaflet of biological membranes. All P4-ATPases in yeast and some in other organisms are required for membrane trafficking; therefore, changes in the transbilayer lipid composition induced by flippases are thought to be crucial for membrane deformation. However, it is poorly understood whether the phospholipid-flipping activity of P4-ATPases can promote membrane deformation. In this study, we assessed membrane deformation induced by flippase activity via monitoring the extent of membrane tubulation using a system that allows inducible recruitment of Bin/amphiphysin/Rvs (BAR) domains to the plasma membrane (PM). Enhanced phosphatidylcholine-flippase activity at the PM due to expression of ATP10A, a member of the P4-ATPase family, promoted membrane tubulation upon recruitment of BAR domains to the PM This is the important evidence that changes in the transbilayer lipid composition induced by P4-ATPases can deform biological membranes.
P4-ATPases 是一种磷脂翻转酶，可将磷脂从生物膜的胞质小叶翻转到质外侧/腔侧。酵母中的所有 P4-ATPases 和其他一些生物中的 P4-ATPases 都需要进行膜运输；因此，翻转酶诱导的跨膜脂质组成的变化被认为对膜变形至关重要。然而，人们对 P4-ATPases 的磷脂翻转活性是否能促进膜变形知之甚少。在这项研究中，我们通过监测膜小管化的程度来评估翻转酶活性诱导的膜变形，该系统允许诱导性募集 Bin/ amphiphysin/Rvs (BAR) 结构域到质膜 (PM)。由于表达 P4-ATPase 家族成员 ATP10A，PM 上的增强的磷脂翻转酶活性促进了 BAR 结构域募集到 PM 后膜小管化的发生。这是 P4-ATPases 诱导的跨膜脂质组成变化可以使生物膜变形的重要证据。
