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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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Citations
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Journal ArticleDOI

The P2Y 6 receptor signals through Gα q /Ca 2+ /PKCα and Gα 13 /ROCK pathways to drive the formation of membrane protrusions and dictate cell migration

TL;DR: Results support the idea that the P2Y6 receptor represents a target of interest to modulate cell migration and revealed an intricate dialogue between two Gα‐protein signaling pathways.
Journal ArticleDOI

Measuring actin flow in 3D cell protrusions.

TL;DR: The implementation of the nanoscale precise imaging by rapid beam oscillation method with a cloverleaf-shaped trajectory in conjunction with the pair cross-correlation function method provides a quantitative way of capturing dynamic flows and organization of proteins during cell migration in 3D in conditions of poor contrast.
Journal ArticleDOI

Extending the molecular clutch beyond actin-based cell motility

TL;DR: This study shows that the molecular clutch hypothesis of how polymerization is transduced into motility via adhesions is a general description of cell movement regardless of the composition of the cytoskeleton.
Journal ArticleDOI

Intracellular Motility: Myosin and Tropomyosin in Actin Cable Flow

TL;DR: Budding yeast contains a minimal component system for elucidating the mechanistic details of retrograde actin flow, which is facilitated by myosin II but is inhibited by a specific tropomyosin isoform (Tpm2p).
Journal ArticleDOI

Mathematical modeling of the impact of actin and keratin filaments on keratinocyte cell spreading

TL;DR: Simulation results confirm the notion that the organization and mechanical properties of cross-linked keratin filaments affect cell spreading and provide details of the kinetics of this effect, and provide further support for the idea that differentiation-related changes in the density and intracellular organization of keratin IFs affect tissue architecture in epidermis and related stratified epithelia.
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.
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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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