Department of Biology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
Dev Cell. 2010 Sep 14;19(3):365-76. doi: 10.1016/j.devcel.2010.08.008.
To maintain mechanical homeostasis, cells must recognize and respond to changes in cytoskeletal integrity. By imaging live cells expressing fluorescently tagged cytoskeletal proteins, we observed that actin stress fibers undergo local, acute, force-induced elongation and thinning events that compromise their stress transmission function, followed by stress fiber repair that restores this capability. The LIM protein zyxin rapidly accumulates at sites of strain-induced stress fiber damage and is essential for stress fiber repair and generation of traction force. Zyxin promotes recruitment of the actin regulatory proteins α-actinin and VASP to compromised stress fiber zones. α-Actinin plays a critical role in restoration of actin integrity at sites of local stress fiber damage, whereas both α-actinin and VASP independently contribute to limiting stress fiber elongation at strain sites, thus promoting stabilization of the stress fiber. Our findings demonstrate a mechanism for rapid repair and maintenance of the structural integrity of the actin cytoskeleton.
为了维持机械内稳态，细胞必须识别和响应细胞骨架完整性的变化。通过对表达荧光标记细胞骨架蛋白的活细胞进行成像，我们观察到肌动蛋白应力纤维会发生局部、急性、力诱导的伸长和变薄事件，从而损害其传递应力的功能，随后进行的应力纤维修复会恢复这种能力。LIM 蛋白黏着斑激酶（zyxin）在应变诱导的应力纤维损伤部位迅速积累，对于应力纤维修复和产生牵引力至关重要。zyxin 促进了肌动蛋白调节蛋白 α-辅肌动蛋白和 VASP 向受损的应力纤维区域的募集。α-辅肌动蛋白在局部应力纤维损伤部位恢复肌动蛋白完整性方面发挥着关键作用，而 α-辅肌动蛋白和 VASP 都可以独立地限制应变部位的应力纤维伸长，从而促进应力纤维的稳定。我们的研究结果表明了一种快速修复和维持肌动蛋白细胞骨架结构完整性的机制。
