Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada.
MEMPHYS, Center for Biomembrane Physics, University of Southern Denmark, Campusvej 55, Odense 5230, Denmark.
Cell Rep. 2018 Jul 24;24(4):1037-1049. doi: 10.1016/j.celrep.2018.06.104.
Mammalian sphingolipids, primarily with C24 or C16 acyl chains, reside in the outer leaflet of the plasma membrane. Curiously, little is known how C24 sphingolipids impact cholesterol and membrane microdomains. Here, we present evidence that C24 sphingomyelin, when placed in the outer leaflet, suppresses microdomains in giant unilamellar vesicles and also suppresses submicron domains in the plasma membrane of HeLa cells. Free energy calculations suggested that cholesterol has a preference for the inner leaflet if C24 sphingomyelin is in the outer leaflet. We indeed observe that cholesterol enriches in the inner leaflet (80%) if C24 sphingomyelin is in the outer leaflet. Similarly, cholesterol primarily resides in the cytoplasmic leaflet (80%) in the plasma membrane of human erythrocytes where C24 sphingolipids are naturally abundant in the outer leaflet. We conclude that C24 sphingomyelin uniquely interacts with cholesterol and regulates the lateral organization in asymmetric membranes, potentially by generating cholesterol asymmetry.
哺乳动物鞘脂主要带有 C24 或 C16 酰基链，位于质膜的外小叶。奇怪的是，对于 C24 鞘脂如何影响胆固醇和膜微区知之甚少。在这里，我们提供的证据表明，在外小叶中存在 C24 神经鞘磷脂时，会抑制巨大单层囊泡中的微区，也会抑制 HeLa 细胞质膜中的亚微米区。自由能计算表明，如果 C24 神经鞘磷脂在外小叶中，胆固醇优先位于内小叶。如果 C24 神经鞘磷脂在外小叶中，我们确实观察到胆固醇在内小叶中富集（80%）。同样，胆固醇主要位于细胞质小叶（80%）中，在人类红细胞的质膜中，C24 鞘脂在外小叶中自然丰富。我们得出的结论是，C24 神经鞘磷脂与胆固醇独特地相互作用，调节不对称膜中的侧向组织，可能通过产生胆固醇不对称性来实现。
