Glenn Honor L, Jacobson Bruce S
Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003l, USA.
Cell Motil Cytoskeleton. 2003 Aug;55(4):265-77. doi: 10.1002/cm.10128.
The adhesion of a cell to its surrounding matrix is a key determinant in many aspects of cell behavior. Adhesion consists of distinct stages : attachment, cell spreading, motility, and/or immobilization. Interrelated signaling pathways regulate these stages, and many adhesion-related signals control the architecture of the cytoskeleton. The various cytoskeletal organizations then give rise to the specific stages of adhesion. It has been shown that arachidonic acid acts at a signaling branch point during cell attachment. Arachidonic acid is metabolized via lipoxygenase to activate actin polymerization and cell spreading. It is also metabolized by cyclooxygenase to generate small actin bundles. We have used confocal microscopy and indirect immunofluorescence to investigate the structure of these cyclooxygenase dependent actin bundles in HeLa cells. We have also employed cell migration assays and pharmacological modulation of cyclooxygenase and downstream signals. The results indicate that cyclooxygenase and PKA stimulate the formation of actin bundles that contain myosin II and associate with small focal adhesions. In addition, we demonstrate that this cytoskeletal organization correlates with increased cell motility.
细胞与其周围基质的黏附是细胞行为诸多方面的关键决定因素。黏附包括不同阶段：附着、细胞铺展、运动和/或固定。相互关联的信号通路调节这些阶段，许多与黏附相关的信号控制细胞骨架的结构。然后，各种细胞骨架组织导致黏附的特定阶段。研究表明，花生四烯酸在细胞附着过程中作用于信号分支点。花生四烯酸通过脂氧合酶代谢以激活肌动蛋白聚合和细胞铺展。它也通过环氧化酶代谢以生成小的肌动蛋白束。我们使用共聚焦显微镜和间接免疫荧光来研究HeLa细胞中这些依赖于环氧化酶的肌动蛋白束的结构。我们还采用了细胞迁移试验以及对环氧化酶和下游信号的药理学调节。结果表明，环氧化酶和蛋白激酶A刺激含有肌球蛋白II并与小的黏着斑相关联的肌动蛋白束的形成。此外，我们证明这种细胞骨架组织与细胞运动性增加相关。
