Homotypic endothelial nanotubes induced by wheat germ agglutinin and thrombin.
Homotypic endothelial nanotubes induced by wheat germ agglutinin and thrombin.
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DOI：
10.1038/s41598-018-25853-3
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发表时间：
2018-05-15
影响因子：
4.6
通讯作者：
McKeown L
中科院分区：
文献类型：
--
作者：
Pedicini L;Miteva KT;Hawley V;Gaunt HJ;Appleby HL;Cubbon RM;Marszalek K;Kearney MT;Beech DJ;McKeown L
内皮屏障的形成是通过连接蛋白的细胞间通讯来维持的。在屏障破坏后维持内皮细胞通讯的机制尚不清楚。众所周知，少量内皮细胞可以通过同型肌动蛋白驱动的隧道纳米管（TNTs）相互连接，这对于血管生理学中的细胞间信息传递至关重要。在这里，我们试图深入了解TNT形成的触发因素。小麦胚芽凝集素是一种c型凝集素，是已知的tnt的标记，出乎意料地引起了tnt的显著诱导。相比之下，琥珀酰化衍生物是无活性的，表明由唾液化蛋白介导。通过sirna介导的敲低，我们发现该蛋白可能是CD31，一种重要的唾液化膜蛋白，通常位于内皮细胞连接处。我们随后认为凝血酶是内皮细胞tnt的生理诱导剂，因为它减少了连接接触。凝血酶减少了连接接触，重新分配了CD31并诱导了TNTs，但其对TNTs的影响与CD31无关。然而，凝血酶诱导的TNT需要PKCα，一种已知的凝血酶依赖性连接重构的介质，这表明在TNT的形成中需要连接蛋白。事实上，小麦胚芽凝集素和凝血酶的tnt诱导效应都与皮质肌动蛋白重排和类似的Ca2+依赖性相关，这表明了共同的潜在机制。一旦形成，Ca2+信号沿着tnt被观察到。
Endothelial barrier formation is maintained by intercellular communication through junctional proteins. The mechanisms involved in maintaining endothelial communication subsequent to barrier disruption remain unclear. It is known that low numbers of endothelial cells can be interconnected by homotypic actin-driven tunneling nanotubes (TNTs) which could be important for intercellular transfer of information in vascular physiology. Here we sought insight into the triggers for TNT formation. Wheat germ agglutinin, a C-type lectin and known label for TNTs, unexpectedly caused striking induction of TNTs. A succinylated derivative was by contrast inactive, suggesting mediation by a sialylated protein. Through siRNA-mediated knockdown we identified that this protein was likely to be CD31, an important sialylated membrane protein normally at endothelial cell junctions. We subsequently considered thrombin as a physiological inducer of endothelial TNTs because it reduces junctional contact. Thrombin reduced junctional contact, redistributed CD31 and induced TNTs, but its effect on TNTs was CD31-independent. Thrombin-induced TNTs nevertheless required PKCα, a known mediator of thrombin-dependent junctional remodelling, suggesting a necessity for junctional proteins in TNT formation. Indeed, TNT-inducing effects of wheat germ agglutinin and thrombin were both correlated with cortical actin rearrangement and similarly Ca2+-dependent, suggesting common underlying mechanisms. Once formed, Ca2+ signalling along TNTs was observed.
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DOI：
10.1083/jcb.201408103
发表时间：
2015-03-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Coon BG;Baeyens N;Han J;Budatha M;Ross TD;Fang JS;Yun S;Thomas JL;Schwartz MA
通讯作者：
Schwartz MA
影响因子：
20.1
作者：
Climent, Montserrat;Quintavalle, Manuela;Elia, Leonardo
通讯作者：
Elia, Leonardo
影响因子：
4.8
作者：
Kouklis, P;Konstantoulaki, M;Malik, AB
通讯作者：
Malik, AB
影响因子：
20.1
作者：
Klarenbach, SW;Chipiuk, A;Murray, AG
通讯作者：
Murray, AG
影响因子：
4.4
作者：
Fifadara, Nimita H.;Beer, Freddy;Ono, Santa J.
通讯作者：
Ono, Santa J.