Loss of Arp2/3 induces an NF-κB-dependent, nonautonomous effect on chemotactic signaling.
Loss of Arp2/3 induces an NF-κB-dependent, nonautonomous effect on chemotactic signaling.
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DOI：
10.1083/jcb.201306032
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发表时间：
2013-12-23
期刊：
影响因子：
--
通讯作者：
Bear JE
中科院分区：
文献类型：
--
作者：
Wu C;Haynes EM;Asokan SB;Simon JM;Sharpless NE;Baldwin AS;Davis IJ;Johnson GL;Bear JE
Arp 2/3水平的降低导致几种分泌因子表达的NF-κ B依赖性增加，从而对趋化性产生非自主性影响。Arp 2/3分支肌动蛋白对细胞骨架动力学和细胞迁移至关重要。然而，影响这个网络的扰动和疾病的表型不能完全用细胞自主效应来解释。在本文中，我们报告Arp 2/3耗尽的非自主效应。我们发现，Arp 2/3耗竭后，许多编码分泌因子（包括趋化因子、生长因子和基质金属蛋白酶）的基因的表达增加，这是一个类似于衰老相关分泌表型的特征。这些因素影响表皮生长因子的趋化性在一个非自主的方式，解决了最近的矛盾Arp 2/3在趋化性的作用。我们证明这些基因被核因子κB通过CCM 2-MEKK 3途径激活，该途径与高渗应激信号传导有关。与此相一致，Arp 2/3耗尽的细胞表现出失调的体积控制和减少肌动蛋白在膜下皮层。在Arp 2/3耗尽的细胞中的渗透信号传导的缺陷可以通过低渗处理来挽救。因此，扰动Arp 2/3有非自主的影响，应考虑在评估实验操作和疾病影响Arp 2/3-肌动蛋白细胞骨架。
A decrease in Arp2/3 levels results in an NF-κB–dependent increase in the expression of several secreted factors, resulting in nonautonomous effects on chemotaxis. Arp2/3-branched actin is critical for cytoskeletal dynamics and cell migration. However, perturbations and diseases affecting this network have phenotypes that cannot be fully explained by cell-autonomous effects. In this paper, we report nonautonomous effects of Arp2/3 depletion. We show that, upon Arp2/3 depletion, the expression of numerous genes encoding secreted factors, including chemokines, growth factors, and matrix metalloproteases, was increased, a signature resembling the senescence-associated secretory phenotype. These factors affected epidermal growth factor chemotaxis in a nonautonomous way, resolving the recent contradictions about the role of Arp2/3 in chemotaxis. We demonstrate that these genes were activated by nuclear factor κB via a CCM2–MEKK3 pathway that has been implicated in hyperosmotic stress signaling. Consistent with this, Arp2/3-depleted cells showed misregulation of volume control and reduced actin in the submembranous cortex. The defects in osmotic signaling in the Arp2/3-depleted cells can be rescued by hypoosmotic treatment. Thus, perturbations of Arp2/3 have nonautonomous effects that should be considered when evaluating experimental manipulations and diseases affecting the Arp2/3-actin cytoskeleton.
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DOI：
10.1038/nrm2890
发表时间：
2010-05
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
16
作者：
Descot, Arnaud;Hoffmann, Reinhard;Posern, Guido
通讯作者：
Posern, Guido
DOI：
10.1159/000059925
发表时间：
1998-01-01
期刊：
CELL VOLUME REGULATION
影响因子：
--
作者：
Moustakas, A;Theodoropoulos, PA;Stournaras, C
通讯作者：
Stournaras, C
影响因子：
16
作者：
Schmidt, C;Peng, BL;Chiao, PJ
通讯作者：
Chiao, PJ
影响因子：
10.5
作者：
Chien, Yuchen;Scuoppo, Claudio;Lowe, Scott W.
通讯作者：
Lowe, Scott W.