Vestweber Dietmar, Zeuschner Dagmar, Rottner Klemens, Schnoor Michael
Department for Vascular Cell Biology; Max-Planck-Institute for Molecular Biomedicine; Münster, Germany.
Actin Dynamics and Motility Unit; Institute of Genetics; University of Bonn; Bonn, Germany ; Helmholtz Centre for Infection Research; Braunschweig, Germany.
Tissue Barriers. 2013 Jan 1;1(1):e23862. doi: 10.4161/tisb.23862.
Cortactin is an actin-binding molecule that regulates various cellular processes requiring actin dynamics. We recently described cortactin-deficient mice and despite its pivotal role for actin remodeling in vitro, these mice are surprisingly healthy. Analyzing cortactin functions in endothelium under inflammatory conditions, we found that cortactin is required for endothelial barrier functions and leukocyte extravasation in vivo. Importantly, these effects were not regulated by defective actin dynamics but instead by a failure to activate the small GTPases Rap1 and RhoG in endothelial cells. Defective RhoG signaling led to reduced ICAM-1 clustering that supported the interaction with leukocytes. These clusters originally seen as rings surrounding adherent leukocytes actually represented in many cases ICAM-1 containing protrusions as they were described before as docking structures. Thus, cortactin is essential for the formation of endothelial docking structures as well as for leukocyte adhesion and extravasation.
皮层肌动蛋白结合蛋白（Cortactin）是一种肌动蛋白结合分子，可调节各种需要肌动蛋白动力学的细胞过程。我们最近描述了缺乏皮层肌动蛋白结合蛋白的小鼠，尽管它在体外对肌动蛋白重塑起着关键作用，但这些小鼠却出奇地健康。在炎症条件下分析皮层肌动蛋白结合蛋白在内皮细胞中的功能时，我们发现皮层肌动蛋白结合蛋白对于体内内皮屏障功能和白细胞外渗是必需的。重要的是，这些作用不是由有缺陷的肌动蛋白动力学调节的，而是由内皮细胞中未能激活小GTP酶Rap1和RhoG所导致的。有缺陷的RhoG信号传导导致细胞间黏附分子-1（ICAM-1）聚集减少，这支持了与白细胞的相互作用。这些最初被视为围绕黏附白细胞的环的簇，在许多情况下实际上代表了含有ICAM-1的突起，正如之前所描述的对接结构。因此，皮层肌动蛋白结合蛋白对于内皮对接结构的形成以及白细胞黏附和外渗至关重要。
