P-selectin mobility undergoes a sol-gel transition as it diffuses from exocytosis sites into the cell membrane.

P-selectin mobility undergoes a sol-gel transition as it diffuses from exocytosis sites into the cell membrane.
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DOI:
10.1038/s41467-022-30669-x
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发表时间:
2022-05-31
影响因子:
16.6
通讯作者:
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中科院分区:
综合性期刊1区
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作为对血管损伤的反应,p -选择素分子被分泌到血管周围的细胞表面。然后它们作为机械锚从血液中捕获白细胞。在这里,我们跟踪在刺激分泌后活内皮细胞表面释放的单个p -选择素分子。我们发现p -选择素最初表现出快速,无限制的扩散,但在几分钟内,运动变得越来越受限,约50%的分子变得完全不动;类似于溶胶-凝胶转变的过程。我们发现去除细胞外c型凝集素结构域(ΔCTLD)和/或细胞内细胞质尾部结构域(ΔCT)对扩散运动具有附加效应,而破坏接头复合体AP2或去除细胞表面硫酸肝素可恢复全长p选择素的迁移率,分别接近ΔCT和ΔCTLD。我们发现p -选择素从胞外作用位点迅速扩散,均匀地装饰细胞表面,但随后变得不那么机动,更适合其机械锚定功能。p -选择素将白细胞招募到血管损伤区域。通过单分子成像,我们发现新分泌的p -选择素在质膜上迅速扩散,然后变得固定化,更适合白细胞捕获。
In response to vascular damage, P-selectin molecules are secreted onto the surface of cells that line our blood vessels. They then serve as mechanical anchors to capture leucocytes from the blood stream. Here, we track individual P-selectin molecules released at the surface of live endothelial cells following stimulated secretion. We find P-selectin initially shows fast, unrestricted diffusion but within a few minutes, movement becomes increasingly restricted and ~50% of the molecules become completely immobile; a process similar to a sol-gel transition. We find removal of the extracellular C-type lectin domain (ΔCTLD) and/or intracellular cytoplasmic tail domain (ΔCT) has additive effects on diffusive motion while disruption of the adapter complex, AP2, or removal of cell-surface heparan sulphate restores mobility of full-length P-selectin close to that of ΔCT and ΔCTLD respectively. We have found P-selectin spreads rapidly from sites of exocytosis and evenly decorates the cell surface, but then becomes less mobile and better-suited to its mechanical anchoring function. P-selectin recruits leucocytes to regions of blood vessel damage. Using single molecule imaging, we find newly secreted P-selectin spreads rapidly across the plasma membrane and then becomes immobilized and better-suited to leucocyte capture.
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