Shuster C B, Herman I M
Department of Biological Sciences, University of Pittsburgh, PA, USA.
Microcirculation. 1998;5(4):239-57.
Alterations in vascular cell shape and motility occur during developmental processes and in response to injury. Similarly, during tumor vascularization and atherogenesis, endothelial and smooth muscle cells undergo motile and proliferative responses to extracellular cues. Recent inroads into our understanding of signal transduction have identified several candidate pathways by which the extracellular matrix- and growth factor-mediated stimulation of vascular cell motility may be mediated. The multiple and divergent extracellular stimuli that stimulate vascular motile responses may converge on the cytoskeleton via a family of ras-related GTPases. Biochemical analyses as well as examination of cytoskeletal dynamics in vivo indicate that actin polymerization at the forward aspects of spreading cytoplasm is capable of driving forward protrusion formation in the absence of a conventional actin motor. Actin polymerization at the plasma membrane of leading lamellae may be mediated both by de novo nucleation of actin filaments and the generation of free filament ends by uncapping the barbed ends of existing actin filaments. This review summarizes the most recent findings in extracellular-cytoskeletal-signal transduction, therein, providing a framework to explain the remarkable remodeling seen in the vasculature during developmental and disease-related processes.
血管细胞形状和运动性的改变发生在发育过程中以及对损伤的反应中。同样，在肿瘤血管生成和动脉粥样硬化形成过程中，内皮细胞和平滑肌细胞会对细胞外信号产生运动性和增殖性反应。最近，我们对信号转导的理解取得了进展，确定了几条候选途径，细胞外基质和生长因子介导的血管细胞运动性刺激可能通过这些途径介导。刺激血管运动反应的多种不同细胞外刺激可能通过一组与ras相关的GTP酶汇聚到细胞骨架上。生化分析以及体内细胞骨架动力学检查表明，在没有传统肌动蛋白马达的情况下，伸展细胞质前端的肌动蛋白聚合能够驱动向前突出的形成。前缘质膜处的肌动蛋白聚合可能由肌动蛋白丝的从头成核以及通过解开现有肌动蛋白丝的带刺末端产生游离丝末端介导。本综述总结了细胞外-细胞骨架-信号转导的最新发现，从而提供一个框架来解释在发育和疾病相关过程中血管系统中所见的显著重塑。
