Developmental Cell：特殊蛋白调节细胞运动
细胞运动可以类比于人的步行过程，反复循环。其中的每个步骤都受到精巧的调节控制，以保证原料和能量的合理利用和细胞迁移的有效进行。现在知道，细胞向前“迈步”（形成前端突出）需要调节细胞运动前端中的片足（lamellipodium）和片层（lamella）两个丝状蛋白网络。Cofilin（丝切蛋白）正是在这一调节中起作用的一个蛋白，以往的研究证明Cofilin是GTPase信号通路下游的一个目标物，它通过核化、解聚和切割F-actin来促使F-actin的循环。但是，至今Cofilin在在前端突出的蛋白网络中确切作用并不为人知道。
美国的科研人员在PtK1细胞首先发现Cofilin在细胞前端的活化（磷酸化状态）是由Pak1控制的，并且证明Pak1/LIMK1信号通路对由Rac-1诱导的细胞前端肌动蛋白纤维网络的再组织是必要的。研究发现，增加Cofilin活性可以影响细胞边缘中F-actin运动并促进形成快速的肌动蛋白纤维逆流。这种加强的快速逆流是由片足的变宽引起的。增加Cofilin活性还可以降低细胞边缘“突出”和“收缩”两个动作的协调性。活化的Cofilin还可以调节F-actin的动力学，也可重新组织细胞运动前端中的片足和片层结构。
活化的的Cofilin在细胞的运动中发挥着广泛而重要的作用，通过接收上游信号，Cofilin重新组织细胞前端的片足和片层结构，从而调节细胞向前“迈步”。
相关论文11月6日发表在爱思唯尔期刊《发育细胞》（Developmental Cell）上。（科学网）
原始出处:
Developmental Cell, Vol 13, 646-662, 06 November 2007
Article
Cofilin Activity Downstream of Pak1 Regulates Cell Protrusion Efficiency by Organizing Lamellipodium and Lamella Actin Networks
Violaine Delorme,1,4 Matthias Machacek,2,4 Céline DerMardirossian,1 Karen L. Anderson,3 Torsten Wittmann,2,5 Dorit Hanein,3 Clare Waterman-Storer,2,6 Gaudenz Danuser,2,
and Gary M. Bokoch1,2,
1 Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
2 Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
3 Infectious Diseases Program, The Burnham Institute for Medical Research, La Jolla, CA 92037, USA
Corresponding author
Gaudenz Danuser
gdanuser@scripps.edu
Corresponding author
Gary M. Bokoch
bokoch@scripps.edu
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.
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