title: ERK reinforces actin polymerization to power persistent edge protrusion during motility.
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.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. michelle.mendoza@ucsf.edu gaudenz.danuser@utsouthwestern.edu.
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Mendoza
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Vilela
authors.affiliation: Departments of Cell and Tissue Biology and Pathology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
authors.forename: Jesus E
authors.initials: JE
authors.lastname: Juarez
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: John
authors.initials: J
authors.lastname: Blenis
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. michelle.mendoza@ucsf.edu gaudenz.danuser@utsouthwestern.edu.
authors.forename: Gaudenz
authors.initials: G
authors.lastname: Danuser
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D001562:Benzimidazoles; D001696:Biomechanical Phenomena; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D022081:Cell Surface Extensions / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007091:Image Processing, Computer-Assisted; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors; D048370:MAP Kinase Kinase 2 / Q000037:antagonists & inhibitors; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008856:Microscopy, Fluorescence / Q000379:methods; D008954:Models, Biological; D058105:Polymerization; D014945:Wound Healing / Q000502:physiology
chemical_list: C517975:AZD 6244; D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D001562:Benzimidazoles; C482128:MAP2K2 protein, human; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2