Chemotaxis in shallow gradients is mediated independently of PtdIns 3-kinase by biased choices between random protrusions

Chemotaxis in shallow gradients is mediated independently of PtdIns 3-kinase by biased choices between random protrusions
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DOI:
10.1038/ncb1536
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发表时间:
2007-02-01
影响因子:
21.3
通讯作者:
Insall, Robert H.
Insall, Robert H.
中科院分区:
生物学1区
文献类型:
--
作者:
Andrew, Natalie;Insall, Robert H.

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目前的真核细胞趋化模型认为,定向感应导致新伪足的局部生成(1)。然而,对伪足发生的定量分析表明,在浅梯度中趋化的机制是根本不同的:第一,多种细胞类型的伪足通常是在现有细胞分叉时产生的,很少从头产生;第二,在浅化学吸引剂梯度中,无论细胞向上还是向下移动,伪足的形成速度都是相同的。新伪足的位置和方向在分叉允许的范围内是随机的,不受化学吸引剂的定向。因此,伪足的产生是独立于趋化信号控制的。第三,定向感知是通过维护最准确的现有伪足来实现的,而不是通过生成新的伪足来实现的。最后,磷脂酰肌醇3-激酶(PI(3)K)抑制剂LY294002影响伪足的产生频率,但不影响选择的准确性,这表明PI(3)K调节细胞运动的基本机制,而不是控制方向。
Current models of eukaryotic chemotaxis propose that directional sensing causes localized generation of new pseudopods(1). However, quantitative analysis of pseudopod generation suggests a fundamentally different mechanism for chemotaxis in shallow gradients: first, pseudopods in multiple cell types are usually generated when existing ones bifurcate and are rarely made de novo; second, in Dictyostelium cells in shallow chemoattractant gradients, pseudopods are made at the same rate whether cells are moving up or down gradients. The location and direction of new pseudopods are random within the range allowed by bifurcation and are not oriented by chemoattractants. Thus, pseudopod generation is controlled independently of chemotactic signalling. Third, directional sensing is mediated by maintaining the most accurate existing pseudopod, rather than through the generation of new ones. Finally, the phosphatidylinositol 3-kinase (PI(3) K) inhibitor LY294002 affects the frequency of pseudopod generation, but not the accuracy of selection, suggesting that PI(3) K regulates the underlying mechanism of cell movement, rather than control of direction.