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Sci Signal. 2015 May 19;8(377):ra47. doi: 10.1126/scisignal.aaa8859.

ERK reinforces actin polymerization to power persistent edge protrusion during motility.

Author information

1
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. michelle.mendoza@ucsf.edu gaudenz.danuser@utsouthwestern.edu.
2
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
3
Departments of Cell and Tissue Biology and Pathology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.

Abstract

Cells move through perpetual protrusion and retraction cycles at the leading edge. These cycles are coordinated with substrate adhesion and retraction of the cell rear. We tracked spatial and temporal fluctuations in the molecular activities of individual moving cells to elucidate how extracellular signal-regulated kinase (ERK) signaling controlled the dynamics of protrusion and retraction cycles. ERK is activated by many cell surface receptors, and we found that ERK signaling specifically reinforced cellular protrusions so that they translated into rapid, sustained forward motion of the leading edge. Using quantitative fluorescent speckle microscopy and cross-correlation analysis, we showed that ERK controlled the rate and timing of actin polymerization by promoting the recruitment of the actin nucleator Arp2/3 to the leading edge. These findings support a model in which surges in ERK activity induced by extracellular cues enhance Arp2/3-mediated actin polymerization to generate protrusion power phases with enough force to counteract increasing membrane tension and to promote sustained motility.

PMID:
25990957
PMCID:
PMC4830495
DOI:
10.1126/scisignal.aaa8859
[Indexed for MEDLINE]
Free PMC Article

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