Millius Arthur, Dandekar Sheel N, Houk Andrew R, Weiner Orion D
Department of Biochemistry, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Curr Biol. 2009 Feb 10;19(3):253-9. doi: 10.1016/j.cub.2008.12.044.
Asymmetric intracellular signals enable cells to migrate in response to external cues. The multiprotein WAVE (also known as SCAR or WASF) complex activates the actin-nucleating Arp2/3 complex [1-4] and localizes to propagating "waves," which direct actin assembly during neutrophil migration [5, 6]. Here, we observe similar WAVE complex dynamics in other mammalian cells and analyze WAVE complex dynamics during establishment of neutrophil polarity. Earlier models proposed that spatially biased generation [7] or selection of protrusions [8] enables chemotaxis. These models require existing morphological polarity to control protrusions. We show that spatially biased generation and selection of WAVE complex recruitment also occur in morphologically unpolarized neutrophils during development of their first protrusions. Additionally, several mechanisms limit WAVE complex recruitment during polarization and movement: Intrinsic cues restrict WAVE complex distribution during establishment of polarity, and asymmetric intracellular signals constrain it in morphologically polarized cells. External gradients can overcome both intrinsic biases and control WAVE complex localization. After latrunculin-mediated inhibition of actin polymerization, addition and removal of agonist gradients globally recruits and releases the WAVE complex from the membrane. Under these conditions, the WAVE complex no longer polarizes, despite the presence of strong external gradients. Thus, actin polymer and the WAVE complex reciprocally interact during polarization.
不对称的细胞内信号使细胞能够响应外部线索而迁移。多蛋白WAVE（也称为SCAR或WASF）复合物激活肌动蛋白成核的Arp2/3复合物[1-4]，并定位于正在传播的“波”，这些“波”在中性粒细胞迁移过程中指导肌动蛋白组装[5,6]。在这里，我们在其他哺乳动物细胞中观察到类似的WAVE复合物动态，并分析中性粒细胞极性建立过程中的WAVE复合物动态。早期模型提出，空间偏向的产生[7]或突起的选择[8]促成趋化作用。这些模型需要现有的形态极性来控制突起。我们表明，在其第一个突起形成过程中，形态上未极化的中性粒细胞中也会发生WAVE复合物募集的空间偏向产生和选择。此外，几种机制在极化和运动过程中限制WAVE复合物募集：内在线索在极性建立过程中限制WAVE复合物分布，不对称的细胞内信号在形态极化的细胞中对其进行限制。外部梯度可以克服内在偏向并控制WAVE复合物定位。在latrunculin介导的肌动蛋白聚合抑制后，激动剂梯度的添加和去除会使WAVE复合物从膜上整体募集和释放。在这些条件下，尽管存在强烈的外部梯度，WAVE复合物不再极化。因此，肌动蛋白聚合物和WAVE复合物在极化过程中相互作用。
