Profilin-1 serves as a gatekeeper for actin assembly by Arp2/3-dependent and -independent pathways.
Profilin-1 serves as a gatekeeper for actin assembly by Arp2/3-dependent and -independent pathways.
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DOI：
10.1016/j.devcel.2014.10.026
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发表时间：
2015-01-12
影响因子：
11.8
通讯作者：
Bear, James E.
中科院分区：
文献类型：
--
作者：
Rotty, Jeremy D.;Wu, Congying;Haynes, Elizabeth M.;Suarez, Cristian;Winkelman, Jonathan D.;Johnson, Heath E.;Haugh, Jason M.;Kovar, David R.;Bear, James E.
细胞包含多种f -肌动蛋白组装途径，包括Arp2/3复合物、形成蛋白和Ena/VASP，这些途径在很大程度上是单独分析的。它们共同从一个共同的g -肌动蛋白池中产生大量的f -肌动蛋白；然而，这些途径之间的相互作用/竞争仍然知之甚少。利用Arpc2条件敲除小鼠的成纤维细胞系，我们建立了具有和不具有Arp2/3复合物的配对细胞。Arpc2 - / -细胞缺乏板足，迁移速度比WT细胞慢，但f -肌动蛋白水平与对照组没有区别。Arpc2−/−细胞中的肌动蛋白组装对细胞松弛素d具有抗性，高度依赖于profin -1和Ena/VASP，但不依赖于formmins。WT细胞中Profilin-1的缺失增加了板足中F-actin和Arp2/3复合物。相反，在体外和体内，外源profin -1的加入抑制了Arp2/3复合物肌动蛋白的成核。这些观察结果表明，细胞中profin -1对Arp2/3复合物的拮抗作用通过平衡Arp2/3复合物依赖和独立的肌动蛋白组装途径来维持肌动蛋白稳态。
Cells contain multiple F-actin assembly pathways including the Arp2/3 complex, formins, and Ena/VASP, which have largely been analyzed separately. They collectively generate the bulk of F-actin from a common pool of G-actin; however, the interplay/competition between these pathways remains poorly understood. Using fibroblast lines derived from an Arpc2 conditional knockout mouse, we established matched-pair cells with and without the Arp2/3 complex. Arpc2−/− cells lack lamellipodia and migrate slower than WT cells, but have F-actin levels indistinguishable from controls. Actin assembly in Arpc2−/− cells was resistant to cytochalasin-D and was highly dependent on profilin-1 and Ena/VASP, but not formins. Profilin-1 depletion in WT cells increased F-actin and Arp2/3 complex in lamellipodia. Conversely, addition of exogenous profilin-1 inhibited Arp2/3 complex actin nucleation in vitro and in vivo. These observations suggest that antagonism of the Arp2/3 complex by profilin-1 in cells maintains actin homeostasis by balancing Arp2/3 complex-dependent and independent actin assembly pathways.
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DOI：
10.1038/nrm2867
发表时间：
2010-04
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
16.2
作者：
Lanier, LM;Gates, MA;Gertler, FB
通讯作者：
Gertler, FB
DOI：
10.1083/jcb.117.5.1023
发表时间：
1992-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Cao LG;Babcock GG;Rubenstein PA;Wang YL
通讯作者：
Wang YL
影响因子：
4.8
作者：
Barzik, M;Kotova, TI;Schafer, DA
通讯作者：
Schafer, DA
影响因子：
3.3
作者：
Mullins, RD;Kelleher, JF;Pollard, TD
通讯作者：
Pollard, TD