Actin microdomains on endothelial cells: association with CD44, ERM proteins, and signaling molecules during quiescence and wound healing
Actin microdomains on endothelial cells: association with CD44, ERM proteins, and signaling molecules during quiescence and wound healing
复制标题
DOI：
10.1007/s00418-004-0648-2
复制
发表时间：
2004-05-01
影响因子：
2.3
通讯作者：
Larsson, LI
中科院分区：
文献类型：
--
作者：
Jensen, PV;Larsson, LI
在培养的内皮细胞中的肌动蛋白细胞骨架的研究中，我们已经观察到，许多细胞的腔侧含有富含透明质酸受体CD 44和埃兹林-根蛋白-膜突蛋白（ERM）蛋白的F-肌动蛋白微区。这些结构域的一小部分也富含酪氨酸磷酸化蛋白和信号分子。大鼠主动脉内皮细胞原位共聚焦显微镜显示，类似的微域发生在体内。在内皮伤口愈合过程中，发生了肌动蛋白细胞骨架的特征性改变。因此，在靠近伤口的许多细胞中，出现了焦点性的F-肌动蛋白分支点。分支点与微结构域相似，它们与CD 44和ERM蛋白共定位，但此外，它们形成肌动蛋白丝分支中心，并与磷酸化蛋白激酶C α/β（II）相关。这些共定位的数据是一致的观点，活化的PKC是负责激活ERM介导的CD 44和肌动蛋白细胞骨架之间的交联。重要的是，PKC活性的抑制减少了磷酸化ERM蛋白的染色，减少了F-肌动蛋白分支点的频率，并抑制了单层伤口愈合。总之，我们的数据表明，内皮细胞含有一种新的肌动蛋白细胞骨架结构，F-肌动蛋白微结构域，并表明在伤口愈合过程中，这种结构与激活的信号分子，从而增强肌动蛋白细胞骨架重塑。
During studies of the actin cytoskeleton in cultured endothelial cells we have observed that the luminal side of many cells contains F-actin microdomains that are rich in the hyaluronan receptor CD44 and in ezrin-radixin-moesin (ERM) proteins. A small subpopulation of the domains are also enriched in tyrosine phosphorylated proteins and signaling molecules. Confocal microscopy of rat aortic endothelial cells in situ demonstrated that similar microdomains occur in vivo. During healing of endothelial wounds, characteristic alterations of the actin cytoskeleton occurred. Thus, in many cells close to the wound, focal F-actin branching points appeared. The branching points were similar to the microdomains in that they colocalized with CD44 and ERM proteins, but, in addition, they formed centers for actin filament branching and were associated with phosphorylated protein kinase C alpha/beta(II). These colocalization data are consonant with the view that activated PKC is responsible for activating ERM-mediated crosslinking between CD44 and the actin cytoskeleton. Importantly, inhibition of PKC activity decreased staining for phosphorylated ERM proteins, decreased the frequency of F-actin branching points, and inhibited monolayer wound healing. Together, our data show that endothelial cells contain a novel actin cytoskeletal structure, the F-actin microdomain, and suggest that during wound healing such structures become associated with activated signaling molecules and thereby enhance actin cytoskeletal remodeling.