Cofilin activity downstream of Pak1 regulates cell protrusion efficiency by organizing lamellipodium and lamella actin networks
Cofilin activity downstream of Pak1 regulates cell protrusion efficiency by organizing lamellipodium and lamella actin networks
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DOI：
10.1016/j.devcel.2007.08.011
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发表时间：
2007-11-01
影响因子：
11.8
通讯作者：
Bokoch, Gary M.
中科院分区：
文献类型：
--
作者：
Delorme, Violaine;Machacek, Matthias;Bokoch, Gary M.
迁移上皮细胞前缘的突出需要精确调节两个肌动蛋白丝（F-肌动蛋白）网络，即片状伪足和片层。 Cofilin 是 Rho GTPase 信号传导的下游靶标，通过其 F-肌动蛋白成核、切断和解聚活性促进 F-肌动蛋白循环。然而，其在调节片状足和片层动力学方面的功能以及这些动力学对突出效率的影响尚不清楚。使用定量荧光散斑显微镜、免疫荧光和电子显微镜，我们确定 Rac1/Pak1/LIMK1 信号通路控制片状足内的丝切蛋白活性。丝切蛋白活性的增强加速了 F-肌动蛋白周转和逆行流动，导致板状伪足变宽。这伴随着片状伪足和片层网络空间重叠的增加以及细胞边缘突出效率的降低。我们提出丝切蛋白通过调节片状足和片层的空间相互作用来充当细胞突出的调节剂。响应上游信号。
Protrusion of the leading edge of migrating epithelial cells requires precise regulation of two actin filament (F-actin) networks, the lamellipodium and the lamella. Cofilin is a downstream target of Rho GTPase signaling that promotes F-actin cycling through its F-actin-nucleating, -severing, and -depolymerizing activity. However, its function in modulating lamellipodium and lamella dynamics, and the implications of these dynamics for protrusion efficiency, has been unclear. Using quantitative fluorescent speckle microscopy, immunofluorescence, and electron microscopy, we establish that the Rac1/Pak1/LIMK1 signaling pathway controls cofilin activity within the lamellipodium. Enhancement of cofilin activity accelerates F-actin turnover and retrograde flow, resulting in widening of the lamellipodium. This is accompanied by increased spatial overlap of the lamellipodium and lamella networks and reduced cell-edge protrusion efficiency. We propose that cofilin functions as a regulator of cell protrusion by modulating the spatial interaction of the lamellipodium and lamella. in response to upstream signals.