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.
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We thank A. Abo, D. Agard, C. Bargmann, D. Drubin, Z. Kam, C. Kenyon, R. Mullins, J. Taunton, J. Weissman, S. Zigmond and members of the Bourne and Sedat laboratories for discussions; A. Abo for the PLB-985 promyelocytic cell line; and C. Bargmann, C. Kenyon, J.V. Small, and S. Zigmond for critical reading of the manuscript. This work was supported in part by grants from the NIH (to H.R.B., J.W.S. and T.J.M.). M.D.W. is a Leukemia Society of America Special Fellow; G.S. is a Medical Research Council of Canada Postdoctoral Fellow; and O.D.W. is an HHMI Predoctoral Fellow.
Correspondence and requests for materials should be addressed to H.R.B.
Supplementary information is available on Nature Cell Biology’s World-Wide Web site (http://cellbio.nature.com).
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Weiner, O., Servant, G., Welch, M. et al. Spatial control of actin polymerization during neutrophil chemotaxis . Nat Cell Biol 1, 75–81 (1999). https://doi.org/10.1038/10042
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