Phospholipids undergo hop diffusion in compartmentalized cell membrane.
Phospholipids undergo hop diffusion in compartmentalized cell membrane.
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DOI：
10.1083/jcb.200202050
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发表时间：
2002-06-10
影响因子：
7.8
通讯作者：
Kusumi, Akihiro
中科院分区：
文献类型：
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作者：
Fujiwara, Takahiro;Ritchie, Ken;Murakoshi, Hideji;Jacobson, Ken;Kusumi, Akihiro
脂质在细胞膜中的扩散速率比在人工双层膜中降低了5 - 100倍。在过去的25年里，这种减速机制一直困扰着细胞生物学家。在此，我们通过在25微秒的时间分辨率下，在单分子水平上研究大鼠肾成纤维细胞中不饱和磷脂的运动来解决这一问题。研究发现细胞膜是分区的：磷脂在跳到相邻分区之前，平均在直径为230纳米（φ）的分区内被限制11毫秒。这些230纳米的分区存在于更大的直径为750纳米的φ分区内，磷脂在其中平均被限制0.33秒。在230纳米分区内的扩散速率为5.4平方微米/秒，这几乎与大的单层脂质体中的扩散速率一样快，这表明细胞膜中扩散速率降低不是因为扩散本身缓慢，而是因为细胞膜在磷脂的侧向扩散方面是分区的。这种分区取决于基于肌动蛋白的膜骨架，但不取决于细胞外基质、膜蛋白的细胞外结构域或富含胆固醇的脂筏。我们提出，各种锚定在基于肌动蛋白的膜骨架网络上的跨膜蛋白起到了一排排栅栏的作用，暂时限制了磷脂。
The diffusion rate of lipids in the cell membrane is reduced by a factor of 5–100 from that in artificial bilayers. This slowing mechanism has puzzled cell biologists for the last 25 yr. Here we address this issue by studying the movement of unsaturated phospholipids in rat kidney fibroblasts at the single molecule level at the temporal resolution of 25 μs. The cell membrane was found to be compartmentalized: phospholipids are confined within 230-nm-diameter (φ) compartments for 11 ms on average before hopping to adjacent compartments. These 230-nm compartments exist within greater 750-nm-φ compartments where these phospholipids are confined for 0.33 s on average. The diffusion rate within 230-nm compartments is 5.4 μm2/s, which is nearly as fast as that in large unilamellar vesicles, indicating that the diffusion in the cell membrane is reduced not because diffusion per se is slow, but because the cell membrane is compartmentalized with regard to lateral diffusion of phospholipids. Such compartmentalization depends on the actin-based membrane skeleton, but not on the extracellular matrix, extracellular domains of membrane proteins, or cholesterol-enriched rafts. We propose that various transmembrane proteins anchored to the actin-based membrane skeleton meshwork act as rows of pickets that temporarily confine phospholipids.