Membrane tension regulates syndecan-1 expression through actin remodelling
Membrane tension regulates syndecan-1 expression through actin remodelling
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DOI：
10.1016/j.bbagen.2019.129413
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发表时间：
2019-11-01
影响因子：
3
通讯作者：
Wang, Wen
中科院分区：
文献类型：
--
作者：
Li, Weiqi;Wang, Wen
背景资料：内皮糖萼位于血管腔界面，是一种富含碳水化合物的复合物，控制着血管的溶质渗透和机械传导等功能。它通过核心蛋白（例如syndecan-1）锚定在细胞膜上，核心蛋白与肌动蛋白细胞骨架偶联。膜张力在膜结合蛋白的重组过程中起着重要的作用，但膜张力对糖萼各组分的影响还知之甚少。方法：采用低渗胁迫研究膜张力对syndecan-1表达的影响。在暴露于低渗培养基20分钟后，内皮糖萼层中多配体蛋白聚糖-1的表达降低至84.7 +/-3.6%（255 mOsm）和64.7 +/-2.1%（167 mOsm）。然而，这种减少是短暂的，在暴露于低渗介质2小时结束时观察到部分恢复。syndecan-1的瞬时减少与肌动蛋白细胞骨架的解聚有关。肌动蛋白操作的效果的进一步检查表明，肌动蛋白解聚细胞松弛素D的结果在持续的syndecan-1减少。相反，使用jasplakinastatin稳定肌动蛋白完全消除了syndecan-1的瞬时减少。结论：我们首次证明，膜张力在syndecan-1表达的调节中起着重要作用，这种作用是由肌动蛋白细胞骨架的重组介导的。这项研究的发现为研究糖萼在血管病理生理学和疾病中的保护作用提供了一个新的场所。
Background: The endothelial glycocalyx, located at the interface of vascular lumen, is a carbohydrate-rich complex that controls vascular functions such as solute permeation and mechanotransduction. It anchors to the cell membrane through core proteins, e.g. syndecan-1, which couple to the actin cytoskeleton. Membrane tension plays an important role in the reorganisation of membrane-bound proteins, however, little is known on the effect of the membrane tension on the various components of the glycocalyx.Methods: Hypo-osmotic stress is used to investigate the effect of the membrane tension on syndecan-1 expression.Results: Following 20 min exposure to hypo-osmotic medium, the expression of syndecan-1 in the endothelial glycocalyx layer is reduced to 84.7 +/- 3.6% (255 mOsm) and 64.7 +/- 2.1% (167 mOsm). This reduction, however, is transient and partial recovery is observed at the end of 2 h exposure to the hypo-osmotic medium. The transient reduction of syndecan-1 is associated with depolymerisation of the actin cytoskeleton. Further examination of the effect of actin manipulation reveals that actin depolymerisation by cytochalasin D results in sustained syndecan-1 reduction. In contrast, stabilising actin using jasplakinolide abolishes the transient reduction of syndecan-1completely.Conclusions: We demonstrate, for the first time, that membrane tension plays an important role in the regulation of syndecan-1 expression and this effect is mediated by the reorganisation of the actin cytoskeleton.General significance: Findings in this study suggest a new venue of research on the protective role of the glycocalyx in vascular pathophysiology and diseases.