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

Dev Cell. 2019 Apr 22;49(2):189-205.e6. doi: 10.1016/j.devcel.2019.03.025.

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.

Keywords: actin network retrograde flow; actin-myosin interaction; cell mechanics; cell migration; cytoskeleton dynamics; myosin light chain phosphorylation; neutrophil chemotaxis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins / metabolism
  • Animals
  • Animals, Genetically Modified
  • Cell Line
  • Cell Movement / physiology
  • Cell Polarity / physiology
  • Cell Surface Extensions / physiology
  • Chemotaxis / physiology*
  • Cytoskeletal Proteins / metabolism
  • Cytoskeleton / metabolism
  • Female
  • Humans
  • Myosin Type II / metabolism
  • Myosin Type II / physiology*
  • Myosins / metabolism
  • Neutrophils / physiology*
  • Zebrafish / metabolism
  • Zebrafish Proteins / metabolism

Substances

  • Actins
  • Cytoskeletal Proteins
  • Zebrafish Proteins
  • Myosin Type II
  • Myosins