@article{6d71b9e225514964a8f1f55ca19d84ca,
title = "Efficient Front-Rear Coupling in Neutrophil Chemotaxis by Dynamic Myosin II Localization",
abstract = "Efficient chemotaxis requires rapid coordination between different parts of the cell in response to changing directional cues. Here, we investigate the mechanism of front-rear coordination in chemotactic neutrophils. We find that changes in the protrusion rate at the cell front are instantaneously coupled to changes in retraction at the cell rear, while myosin II accumulation at the rear exhibits a reproducible 9–15-s lag. In turning cells, myosin II exhibits dynamic side-to-side relocalization at the cell rear in response to turning of the leading edge and facilitates efficient turning by rapidly re-orienting the rear. These manifestations of front-rear coupling can be explained by a simple quantitative model incorporating reversible actin-myosin interactions with a rearward-flowing actin network. Finally, the system can be tuned by the degree of myosin regulatory light chain (MRLC) phosphorylation, which appears to be set in an optimal range to balance persistence of movement and turning ability. Efficient chemotaxis requires close coordination between the front and the rear of a migrating cell. Tsai et al. identified a mechanical feedback between front protrusion and rear retraction, mediated by cell-scale retrograde flow, membrane tension, and dynamic myosin relocalization that is optimized to balance migration persistence with turning efficiency.",
keywords = "actin network retrograde flow, actin-myosin interaction, cell mechanics, cell migration, cytoskeleton dynamics, myosin light chain phosphorylation, neutrophil chemotaxis",
author = "Tsai, {Tony Y.C.} and Collins, {Sean R.} and Chan, {Caleb K.} and Amalia Hadjitheodorou and Lam, {Pui Ying} and Lou, {Sunny S.} and Yang, {Hee Won} and Julianne Jorgensen and Felix Ellett and Daniel Irimia and Davidson, {Michael W.} and Fischer, {Robert S.} and Anna Huttenlocher and Tobias Meyer and Ferrell, {James E.} and Theriot, {Julie A.}",
note = "Funding Information: We dedicate this paper to the memory of M.W.D. We thank Emmanuel Guignet for training on HL60 cell culture and electroporation, Orion Weiner for the HL60 cells expressing actin-YFP, Xuedong Liu for the FG46013 vector for lentivirus production, and Zachary Pincus for developing Celltool. Several of our experiments with microfabricated devices not presented in this manuscript have generated great insights on the mechanics of HL60 migration. These devices were made available through collaborations with Sangmoo Jeong and Yi Cui at Stanford University and Alex Groisman and Micha Adler at the University of California at San Diego. We thank Lucien Weiss, Thomas Wilson, and W.E. Moerner for help with microscopy and Alex Mogilner and Kun-Chun Lee for help with the mathematical model. Finally, we would like to thank Kinneret Keren, Cyrus Wilson, Orion Weiner, James Spudich, Jagesh Shah, Harrison Prentice-Mott, and members of the Theriot and Ferrell labs for helpful discussions and Michelle Rengarajan and Lena Koslover for comments on the manuscript. This work was supported by the Howard Hughes Medical Institute (J.A.T.), the National Institutes of Health (GM046383 to J.E.F. GM092804 and EB002503 to D.I. and GM074827 to A. Huttenlocher), and by fellowships from the Smith Foundation and Baxter Foundation to T.Y.-C.T. the Helen Hay Whitney Foundation to S.R.C. the Croucher Foundation Joint Universities Summer Teaching Laboratory (JUSTL) program to P-Y.L. Shriners Hospital for Children to F.E. and the BioX Bowes Fellowship and the Alexander S. Onassis Public Benefit Foundation to A. Hadjitheodorou. C.K.C. was supported by the Stanford Cellular and Molecular Biology Training Grant (NIH T32-GM007276) and S S.L. was supported by the Stanford Medical Scientist Training Program (NIH T32-GM007365). Work in the laboratories of T.M. J.E.F. and J.A.T. is supported by an NIH program project grant to the Stanford Center for Systems Biology (P50 GM107615). T.Y.-C.T. J.E.F. and J.A.T. designed the majority of the experiments. T.Y.-C.T. S.R.C. C.K.C. A. Hadjitheodorou. P.-Y.L. S.S.L. and H.W.Y. performed the experiments. S.R.C. H.W.Y. and T.M. designed the RhoA sensor experiments. J.J. F.E. and D.I. designed the microfluidic device. P.-Y.L. R.S.F. and A. Huttenlocher designed the zebrafish experiments, T.Y.-C.T. C.K.C. and A. Hadjitheodorou analyzed the data. M.W.D. provided reagents. T.Y.-C.T. and J.A.T. wrote the manuscript with assistance from all authors. The authors declare no competing interests. Funding Information: We dedicate this paper to the memory of M.W.D. We thank Emmanuel Guignet for training on HL60 cell culture and electroporation, Orion Weiner for the HL60 cells expressing actin-YFP, Xuedong Liu for the FG46013 vector for lentivirus production, and Zachary Pincus for developing Celltool. Several of our experiments with microfabricated devices not presented in this manuscript have generated great insights on the mechanics of HL60 migration. These devices were made available through collaborations with Sangmoo Jeong and Yi Cui at Stanford University and Alex Groisman and Micha Adler at the University of California at San Diego. We thank Lucien Weiss, Thomas Wilson, and W.E. Moerner for help with microscopy and Alex Mogilner and Kun-Chun Lee for help with the mathematical model. Finally, we would like to thank Kinneret Keren, Cyrus Wilson, Orion Weiner, James Spudich, Jagesh Shah, Harrison Prentice-Mott, and members of the Theriot and Ferrell labs for helpful discussions and Michelle Rengarajan and Lena Koslover for comments on the manuscript. This work was supported by the Howard Hughes Medical Institute (J.A.T.), the National Institutes of Health ( GM046383 to J.E.F., GM092804 and EB002503 to D.I., and GM074827 to A. Huttenlocher), and by fellowships from the Smith Foundation and Baxter Foundation to T.Y.-C.T., the Helen Hay Whitney Foundation to S.R.C., the Croucher Foundation Joint Universities Summer Teaching Laboratory (JUSTL) program to P-Y.L., Shriners Hospital for Children to F.E., and the BioX Bowes Fellowship and the Alexander S. Onassis Public Benefit Foundation to A. Hadjitheodorou. C.K.C. was supported by the Stanford Cellular and Molecular Biology Training Grant (NIH T32-GM007276 ) and S S.L. was supported by the Stanford Medical Scientist Training Program (NIH T32-GM007365 ). Work in the laboratories of T.M., J.E.F., and J.A.T. is supported by an NIH program project grant to the Stanford Center for Systems Biology ( P50 GM107615 ). Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = apr,
day = "22",
doi = "10.1016/j.devcel.2019.03.025",
language = "English",
volume = "49",
pages = "189--205.e6",
journal = "Developmental Cell",
issn = "1534-5807",
number = "2",
}