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Two distinct actin networks drive the protrusion of migrating cells

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TLDR
Computational analysis of fluorescent speckle microscopy movies of migrating epithelial cells revealed this process is mediated by two spatially colocalized but kinematically, kinetically, molecularly, and functionally distinct actin networks.
Abstract
Cell migration initiates by extension of the actin cytoskeleton at the leading edge. Computational analysis of fluorescent speckle microscopy movies of migrating epithelial cells revealed this process is mediated by two spatially colocalized but kinematically, kinetically, molecularly, and functionally distinct actin networks. A lamellipodium network assembled at the leading edge but completely disassembled within 1 to 3 micrometers. It was weakly coupled to the rest of the cytoskeleton and promoted the random protrusion and retraction of the leading edge. Productive cell advance was a function of the second colocalized network, the lamella, where actomyosin contraction was integrated with substrate adhesion.

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Journal ArticleDOI

Actin polymerization downstream of integrins: signaling pathways and mechanotransduction

TL;DR: This review describes the major actin regulators, Ena/VASP proteins, formins and Arp2/3 complexes, in the context of signaling pathways downstream of integrins, and focuses on the specific signaling pathways that transduce the rigidity of the substrate and which control durotaxis, i.e. directed migration of cells towards increased ECM rigidity.
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Arp2 depletion inhibits sheet-like protrusions but not linear protrusions of fibroblasts and lymphocytes.

TL;DR: It is concluded that Arp2/3 complex plays a significant role in assembly of sheet-like protrusions, especially during early stages of cell spreading, but is not required for assembly of a variety of linear actin-based protrusion.
Journal ArticleDOI

alpha-Crystallin localizes to the leading edges of migrating lens epithelial cells.

TL;DR: This is the first report demonstrating specific localization of αA and αB-crystallins to the lamellipodia in migrating lens epithelial cells, and indicates a potential role for α- Crystallin in actin dynamics during cell migration.
Journal ArticleDOI

An open model of actin dendritic nucleation.

TL;DR: This work presents a comprehensive model that integrates and unifies much of the in vitro data on the components of the dendritic nucleation mechanism for actin dynamics, and can be accessed, analyzed, modified, and extended.
References
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Journal ArticleDOI

Cell Migration: A Physically Integrated Molecular Process

TL;DR: The authors are grateful for financial support from the National Institutes of Health (grants GM23244 and GM53905), and to very helpful comments on the manuscript from Elliot Elson, Vlodya Gelfand, Paul Matsudaira, Julie Theriot, and Sally Zigmond.
Journal ArticleDOI

Cellular Motility Driven by Assembly and Disassembly of Actin Filaments

TL;DR: A core set of proteins including actin, Arp2/3 complex, profilin, capping protein, and ADF/cofilin can reconstitute the process in vitro, and mathematical models of the constituent reactions predict the rate of motion.
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The interaction of Arp2/3 complex with actin: Nucleation, high affinity pointed end capping, and formation of branching networks of filaments

TL;DR: It is shown that Arp2/3 complex purified from Acanthamoeba caps the pointed ends of actin filaments with high affinity and increases the critical concentration for polymerization at the pointed end from 0.6 to 1.0 microM.
Journal ArticleDOI

Dissecting Temporal and Spatial Control of Cytokinesis with a Myosin II Inhibitor

TL;DR: It is shown that exit from the cytokinetic phase of the cell cycle depends on ubiquitin-mediated proteolysis and continuous signals from microtubules are required to maintain the position of the cleavage furrow, and these signals control the localization of myosin II independently of other furrow components.
Journal ArticleDOI

Actions of cytochalasins on the organization of actin filaments and microtubules in a neuronal growth cone.

TL;DR: Results suggest that actin normally polymerizes at the leading edge and then flows rearward at a rate between 3-6 microns/min, which is consistent with their being secondary to effects of CB on lamellar F-actin.
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