Sphingolipid Organization in the Plasma Membrane and the Mechanisms That Influence It.
Sphingolipid Organization in the Plasma Membrane and the Mechanisms That Influence It.
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质膜中的鞘脂组织及其影响它的机制。
DOI：
10.3389/fcell.2016.00154
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发表时间：
2016
影响因子：
5.5
通讯作者：
Kraft ML
中科院分区：
文献类型：
--
作者：
Kraft ML
鞘脂是真核细胞质膜的结构成分。它们的代谢产生调节基本细胞过程的生物活性信号分子。鞘脂分离成不同的膜结构域可能对细胞功能至关重要。本文介绍了鞘脂分布在哺乳动物细胞质膜的早期研究，塑造了最流行的当前模型的质膜组织。鞘脂分布在刺激和静息细胞的传统成像研究的结果进行了说明。这些数据与先进的成像技术，包括超分辨率荧光检测和高分辨率二次离子质谱（西姆斯）获得的最新结果进行了比较。重点放在新的洞察鞘脂组织内的质膜，从直接成像的稳定同位素标记的脂质在实际的细胞膜与高分辨率的西姆斯。超分辨率荧光技术最近揭示了鞘脂的生物物理行为和胆固醇类似物在活细胞膜中的不受阻碍的扩散最终与质膜组织的流行假设模型形成对比。高分辨率西姆斯研究也与流行的假设相冲突，显示鞘脂集中在微米级的膜结构域中，但胆固醇均匀分布在质膜内。细胞胆固醇的减少减少了质膜中鞘脂结构域的数量，而细胞骨架的破坏消除了它们。此外，血凝素，跨膜蛋白，被认为是一个假定的筏标记，没有集群内鞘脂富集区的质膜。因此，鞘脂在质膜上的分布依赖于细胞骨架，而不是与胆固醇或血凝素的有利相互作用。这些研究结果所建议的质膜组织的替代观点进行了讨论。
Sphingolipids are structural components in the plasma membranes of eukaryotic cells. Their metabolism produces bioactive signaling molecules that modulate fundamental cellular processes. The segregation of sphingolipids into distinct membrane domains is likely essential for cellular function. This review presents the early studies of sphingolipid distribution in the plasma membranes of mammalian cells that shaped the most popular current model of plasma membrane organization. The results of traditional imaging studies of sphingolipid distribution in stimulated and resting cells are described. These data are compared with recent results obtained with advanced imaging techniques, including super-resolution fluorescence detection and high-resolution secondary ion mass spectrometry (SIMS). Emphasis is placed on the new insight into the sphingolipid organization within the plasma membrane that has resulted from the direct imaging of stable isotope-labeled lipids in actual cell membranes with high-resolution SIMS. Super-resolution fluorescence techniques have recently revealed the biophysical behaviors of sphingolipids and the unhindered diffusion of cholesterol analogs in the membranes of living cells are ultimately in contrast to the prevailing hypothetical model of plasma membrane organization. High-resolution SIMS studies also conflicted with the prevailing hypothesis, showing sphingolipids are concentrated in micrometer-scale membrane domains, but cholesterol is evenly distributed within the plasma membrane. Reductions in cellular cholesterol decreased the number of sphingolipid domains in the plasma membrane, whereas disruption of the cytoskeleton eliminated them. In addition, hemagglutinin, a transmembrane protein that is thought to be a putative raft marker, did not cluster within sphingolipid-enriched regions in the plasma membrane. Thus, sphingolipid distribution in the plasma membrane is dependent on the cytoskeleton, but not on favorable interactions with cholesterol or hemagglutinin. The alternate views of plasma membrane organization suggested by these findings are discussed.