Efficient Front-Rear Coupling in Neutrophil Chemotaxis by Dynamic Myosin II Localization

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 c...

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Veröffentlicht in:Developmental cell 2019-04, Vol.49 (2), p.189-205.e6
Hauptverfasser: Tsai, Tony Y.-C., Collins, Sean R., Chan, Caleb K., Hadjitheodorou, Amalia, Lam, Pui-Ying, Lou, Sunny S., Yang, Hee Won, Jorgensen, Julianne, Ellett, Felix, Irimia, Daniel, Davidson, Michael W., Fischer, Robert S., Huttenlocher, Anna, Meyer, Tobias, Ferrell, James E., Theriot, Julie A.
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Sprache:eng
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Zusammenfassung: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. [Display omitted] •Front protrusion and rear retraction are tightly coupled in migrating neutrophils•Mechanical model explains observed time lag of myosin accumulation at the cell rear•Dynamic myosin relocalization facilitates efficient cell turning•Myosin dynamics optimized to balance migration persistence and cell turning efficiency 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.
ISSN:1534-5807
1878-1551
DOI:10.1016/j.devcel.2019.03.025