A role for Cdc42 in macrophage chemotaxis.

A role for Cdc42 in macrophage chemotaxis.
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DOI:
10.1083/jcb.141.5.1147
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发表时间:
1998-06-01
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Jones GE
Jones GE
中科院分区:
其他
文献类型:
--
作者:
Allen WE;Zicha D;Ridley AJ;Jones GE

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已知Rho家族的三个成员Cdc 42、Rac和Rho调节基于肌动蛋白的细胞骨架结构的组织。在Bac1.2F5巨噬细胞中,我们已经表明,Rho调节细胞收缩,而Rac和Cdc 42分别调节板状伪足和丝状伪足的形成。我们现在已经测试了Cdc 42,Rac和Rho在集落刺激因子-1(CSF-1)诱导的巨噬细胞迁移和使用Dunn趋化室的趋化性中的作用。显微注射组成性激活的RhoA,Rac 1,或Cdc 42抑制细胞迁移,大概是因为细胞不能显着响应CSF-1。CSF-1诱导的迁移需要Rho和Rac,因为在注射C3转移酶(Rho的抑制剂)或显性阴性Rac突变体N17 Rac 1的细胞中,迁移速度降低至背景水平。与此相反,细胞注射显性负Cdc 42突变体,N17 Cdc 42,能够迁移,但不沿梯度方向移动,并对CSF-1的趋化性被废除。我们的结论是,Rho和Rac的细胞迁移的过程中所需的,而Cdc 42是所需的细胞响应于梯度的CSF-1,但不是必不可少的细胞运动。
Three members of the Rho family, Cdc42, Rac, and Rho are known to regulate the organization of actin-based cytoskeletal structures. In Bac1.2F5 macrophages, we have shown that Rho regulates cell contraction, whereas Rac and Cdc42 regulate the formation of lamellipodia and filopodia, respectively. We have now tested the roles of Cdc42, Rac, and Rho in colony stimulating factor-1 (CSF-1)–induced macrophage migration and chemotaxis using the Dunn chemotaxis chamber. Microinjection of constitutively activated RhoA, Rac1, or Cdc42 inhibited cell migration, presumably because the cells were unable to polarize significantly in response to CSF-1. Both Rho and Rac were required for CSF-1–induced migration, since migration speed was reduced to background levels in cells injected with C3 transferase, an inhibitor of Rho, or with the dominant-negative Rac mutant, N17Rac1. In contrast, cells injected with the dominant-negative Cdc42 mutant, N17Cdc42, were able to migrate but did not polarize in the direction of the gradient, and chemotaxis towards CSF-1 was abolished. We conclude that Rho and Rac are required for the process of cell migration, whereas Cdc42 is required for cells to respond to a gradient of CSF-1 but is not essential for cell locomotion.
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