Erk regulation of actin capping and bundling by Eps8 promotes cortex tension and leader bleb-based migration
Jeremy S Logue,
Alexander X Cartagena-Rivera,
Michelle A Baird,
Michael W Davidson,
Richard S Chadwick,
Clare M Waterman
Affiliations
Jeremy S Logue
National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, United States; National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, United States
Alexander X Cartagena-Rivera
National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, United States
Michelle A Baird
National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, United States
Michael W Davidson
National High Magnetic Field Laboratory and Department of Biological Science, Florida State University, Tallahassee, United States
Richard S Chadwick
National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, United States
Clare M Waterman
National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, United States
Within the confines of tissues, cancer cells can use blebs to migrate. Eps8 is an actin bundling and capping protein whose capping activity is inhibited by Erk, a key MAP kinase that is activated by oncogenic signaling. We tested the hypothesis that Eps8 acts as an Erk effector to modulate actin cortex mechanics and thereby mediate bleb-based migration of cancer cells. Cells confined in a non-adhesive environment migrate in the direction of a very large ‘leader bleb.’ Eps8 bundling activity promotes cortex tension and intracellular pressure to drive leader bleb formation. Eps8 capping and bundling activities act antagonistically to organize actin within leader blebs, and Erk mediates this effect. An Erk biosensor reveals concentrated kinase activity within leader blebs. Bleb contents are trapped by the narrow neck that separates the leader bleb from the cell body. Thus, Erk activity promotes actin bundling by Eps8 to enhance cortex tension and drive the bleb-based migration of cancer cells under non-adhesive confinement.
