Research Article

Membrane-proximal F-actin restricts local membrane protrusions and directs cell migration

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Science  12 Jun 2020:
Vol. 368, Issue 6496, pp. 1205-1210
DOI: 10.1126/science.aay7794

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Actin cortex controls cell migration

Cell migration is mainly controlled by local actin polymerization–driven membrane protrusion. However, a second structural mechanism might also regulate membrane protrusions and directed migration: changes in the density of the attachment between the plasma membrane and the underlying F-actin cortex, a parameter related to membrane tension. Many types of attachment and signaling mechanisms are known to alter the density of membrane-proximal cortical actin. Bisaria et al. designed a membrane-proximal F-actin (MPA) reporter that could directly measure local changes in the density of MPA in living cells. Levels of MPA were surprisingly low toward the front of migrating cells despite an opposing high overall concentration of F-actin in the same front region. The researchers propose that MPA density can integrate different signaling processes to direct local membrane protrusions and stabilize cell polarity during cell migration.

Science, this issue p. 1205

Abstract

Cell migration is driven by local membrane protrusion through directed polymerization of F-actin at the front. However, F-actin next to the plasma membrane also tethers the membrane and thus resists outgoing protrusions. Here, we developed a fluorescent reporter to monitor changes in the density of membrane-proximal F-actin (MPA) during membrane protrusion and cell migration. Unlike the total F-actin concentration, which was high in the front of migrating cells, MPA density was low in the front and high in the back. Back-to-front MPA density gradients were controlled by higher cofilin-mediated turnover of F-actin in the front. Furthermore, nascent membrane protrusions selectively extended outward from areas where MPA density was reduced. Thus, locally low MPA density directs local membrane protrusions and stabilizes cell polarization during cell migration.

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