Ceramide selectively displaces cholesterol from ordered lipid domains (rafts) - Implications for lipid raft structure and function
Ceramide selectively displaces cholesterol from ordered lipid domains (rafts) - Implications for lipid raft structure and function
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DOI：
10.1074/jbc.m309992200
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发表时间：
2004-03-12
影响因子：
4.8
通讯作者：
London, E
中科院分区：
文献类型：
--
作者：
London, M;London, E
神经酰胺是一种膜脂，参与许多重要的生物过程。最近的证据表明，神经酰胺可能存在于脂筏内并在脂筏内发挥作用;据信许多真核细胞膜内存在有序的鞘脂和富含胆固醇的脂质结构域。使用脂质囊泡含有共存的筏域和无序的流体域，我们发现，天然和饱和的合成神经酰胺取代甾醇筏。其他筏脂质仍然筏相关的神经酰胺的存在下，显示位移是相对具体的甾醇。像含胆固醇的筏一样，富含神经酰胺的“筏”保持高度有序的状态。天然神经酰胺与饱和二酸甘油酯和不饱和神经酰胺的固醇置换能力的比较表明，紧密的脂质堆积对于神经酰胺置换固醇至关重要。基于这些结果，以及胆固醇和神经酰胺都具有小的极性头基的事实，我们提出，神经酰胺和胆固醇竞争与筏的关联，因为筏脂质与大的头基，以容纳小的头基脂质的方式，防止不利的接触的小的头基脂质和周围的水性环境的烃基之间的能力有限。尽量减少胆固醇和神经酰胺与水的接触可能是其他分子与筏结合的强大驱动力。此外，从筏置换甾醇的神经酰胺是很可能有显着的影响筏的结构和功能，改变液体有序的性质以及分子组成。在这方面，某些先前观察到的生理过程可能是位移的结果。特别是，提出了一个直接连接到以前观察到的鞘磷脂酶诱导的位移的胆固醇从细胞质膜。
Ceramide is a membrane lipid involved in a number of crucial biological processes. Recent evidence suggests that ceramide is likely to reside and function within lipid rafts; ordered sphingolipid and cholesterol-rich lipid domains believed to exist within many eukaryotic cell membranes. Using lipid vesicles containing co-existing raft domains and disordered fluid domains, we find that natural and saturated synthetic ceramides displace sterols from rafts. Other raft lipids remain raft-associated in the presence of ceramide, showing displacement is relatively specific for sterols. Like cholesterol-containing rafts, ceramide-rich "rafts" remain in a highly ordered state. Comparison of the sterol-displacing abilities of natural ceramides with those of saturated diglycerides and an unsaturated ceramide demonstrates that tight lipid packing is critical for sterol displacement by ceramide. Based on these results, and the fact that cholesterol and ceramides both have small polar headgroups, we propose that ceramides and cholesterol compete for association with rafts because of a limited capacity of raft lipids with large headgroups to accommodate small headgroup lipids in a manner that prevents unfavorable contact between the hydrocarbon groups of the small headgroup lipids and the surrounding aqueous environment. Minimizing the exposure of cholesterol and ceramide to water may be a strong driving force for the association of other molecules with rafts. Furthermore, displacement of sterol from rafts by ceramide is very likely to have marked effects upon raft structure and function, altering liquid ordered properties as well as molecular composition. In this regard, certain previously observed physiological processes may be a result of displacement. In particular, a direct connection to the previously observed sphingomyelinase-induced displacement of cholesterol from plasma membranes in cells is proposed.