An Actin-Based Wave Generator Organizes Cell Motility

Abstract

Although many of the regulators of actin assembly are known, we do not understand how these components act together to organize cell shape and movement. To address this question, we analyzed the spatial dynamics of a key actin regulator—the Scar/WAVE complex—which plays an important role in regulating cell shape in both metazoans and plants. We have recently discovered that the Hem-1/Nap1 component of the Scar/WAVE complex localizes to propagating waves that appear to organize the leading edge of a motile immune cell, the human neutrophil. Actin is both an output and input to the Scar/WAVE complex: the complex stimulates actin assembly, and actin polymer is also required to remove the complex from the membrane. These reciprocal interactions appear to generate propagated waves of actin nucleation that exhibit many of the properties of morphogenesis in motile cells, such as the ability of cells to flow around barriers and the intricate spatial organization of protrusion at the leading edge. We propose that cell motility results from the collective behavior of multiple self-organizing waves.

The Drosophila Arf1 homologue Arf79F is essential for lamellipodium formation

“…While both inhibitors abrogated lamellipodium formation, cell cortex Sra1 still remained in ,44% of LatB-treated cells and ,51% of CytoD-treated cells (insets) demonstrating that Sra1 still localised to the cell periphery upon inhibition of lamellipodial actin polymerisation. Consistent with our finding, WRC components have been previously observed at the plasma membrane of mammalian cell treated with LatB (Weiner et al, 2007).…”

Phase geometries of two-dimensional excitable waves govern self-organized morphodynamics of amoeboid cells

“…Future studies that include mutant analysis should allow comparison of details that delineate the existing models. Also of theoretical interest is to relate similar waves of PIP3 and/or F-actin observed in animal cells (7,(36)(37)(38) and other amoeba species (28). Although other feedback mechanisms in For weak feedback strength, waves were extinguished at the boundary so that they propagated only transiently as observed in LY294002-treated cells (Fig.…”

Cytoskeletal control of B cell responses to antigens

“…In B cells, the WAVE complex is composed of WASF2 and four other proteins (CYFIP2, NCKAP1L, ABI1, BRK1) 66 . The unique property of the WAVE complex is that it produces spreading arcs of branched actin polymerization, which promote the formation of lamellipodia 67,68 . The WAVE complex is activated by RAC GTPases via VAV proteins and by binding to PIP3 at the plasma membrane 10 .…”