Weiner O D, Servant G, Welch M D, Mitchison T J, Sedat J W, Bourne H R
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0554, USA.
Nat Cell Biol. 1999 Jun;1(2):75-81. doi: 10.1038/10042.
Neutrophils respond to chemotactic stimuli by increasing the nucleation and polymerization of actin filaments, but the location and regulation of these processes are not well understood. Here, using a permeabilized-cell assay, we show that chemotactic stimuli cause neutrophils to organize many discrete sites of actin polymerization, the distribution of which is biased by external chemotactic gradients. Furthermore, the Arp2/3 complex, which can nucleate actin polymerization, dynamically redistributes to the region of living neutrophils that receives maximal chemotactic stimulation, and the least-extractable pool of the Arp2/3 complex co-localizes with sites of actin polymerization. Our observations indicate that chemoattractant-stimulated neutrophils may establish discrete foci of actin polymerization that are similar to those generated at the posterior surface of the intracellular bacterium Listeria monocytogenes. We propose that asymmetrical establishment and/or maintenance of sites of actin polymerization produces directional migration of neutrophils in response to chemotactic gradients.
中性粒细胞通过增加肌动蛋白丝的成核和聚合来响应趋化刺激,但这些过程的位置和调控尚未完全明确。在此,我们利用透化细胞检测法表明,趋化刺激会使中性粒细胞组织许多离散的肌动蛋白聚合位点,其分布受外部趋化梯度的影响而产生偏向性。此外,能够引发肌动蛋白聚合的Arp2/3复合体动态重新分布到接受最大趋化刺激的活中性粒细胞区域,且Arp2/3复合体中最难提取的部分与肌动蛋白聚合位点共定位。我们的观察结果表明,趋化因子刺激的中性粒细胞可能会形成与细胞内细菌单核细胞增生李斯特菌后表面产生的那些类似的离散肌动蛋白聚合焦点。我们提出,肌动蛋白聚合位点的不对称建立和/或维持会促使中性粒细胞响应趋化梯度进行定向迁移。