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      Keeping in touch with contact inhibition of locomotion

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      Trends in Cell Biology
      Elsevier Science Publishers

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          Abstract

          Contact inhibition of locomotion (CIL) is the process by which cells in vitro change their direction of migration upon contact with another cell. Here, we revisit the concept that CIL plays a central role in the migration of single cells and in collective migration, during both health and disease. Importantly, malignant cells exhibit a diminished CIL behaviour which allows them to invade healthy tissues. Accumulating evidence indicates that CIL occurs in vivo and that regulation of small Rho GTPases is important in the collapse of cell protrusions upon cell contact, the first step of CIL. Finally, we propose possible cell surface proteins that could be involved in the initial contact that regulates Rho GTPases during CIL.

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          Most cited references70

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          Cellular motility driven by assembly and disassembly of actin filaments.

          Motile cells extend a leading edge by assembling a branched network of actin filaments that produces physical force as the polymers grow beneath the plasma membrane. 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. Signaling pathways converging on WASp/Scar proteins regulate the activity of Arp2/3 complex, which mediates the initiation of new filaments as branches on preexisting filaments. After a brief spurt of growth, capping protein terminates the elongation of the filaments. After filaments have aged by hydrolysis of their bound ATP and dissociation of the gamma phosphate, ADF/cofilin proteins promote debranching and depolymerization. Profilin catalyzes the exchange of ADP for ATP, refilling the pool of ATP-actin monomers bound to profilin, ready for elongation.
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            Coordination of Rho GTPase activities during cell protrusion

            The GTPases Rac1, RhoA and Cdc42 act in concert to control cytoskeleton dynamics1-3. Recent biosensor studies have shown that all three GTPases are activated at the front of migrating cells4-7 and biochemical evidence suggests that they may regulate one another: Cdc42 can activate Rac18, and Rac1 and RhoA are mutually inhibitory9-12. However, their spatiotemporal coordination, at the seconds and single micron dimensions typical of individual protrusion events, remains unknown. Here, we examine GTPase coordination both through simultaneous visualization of two GTPase biosensors and using a “computational multiplexing” approach capable of defining the relationships between multiple protein activities visualized in separate experiments. We found that RhoA is activated at the cell edge synchronous with edge advancement, whereas Cdc42 and Rac1 are activated 2 μm behind the edge with a delay of 40 sec. This indicates that Rac1 and RhoA operate antagonistically through spatial separation and precise timing, and that RhoA plays a role in the initial events of protrusion, while Rac1 and Cdc42 activate pathways implicated in reinforcement and stabilization of newly expanded protrusions.
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              Random versus directionally persistent cell migration.

              Directional migration is an important component of cell motility. Although the basic mechanisms of random cell movement are well characterized, no single model explains the complex regulation of directional migration. Multiple factors operate at each step of cell migration to stabilize lamellipodia and maintain directional migration. Factors such as the topography of the extracellular matrix, the cellular polarity machinery, receptor signalling, integrin trafficking, integrin co-receptors and actomyosin contraction converge on regulation of the Rho family of GTPases and the control of lamellipodial protrusions to promote directional migration.
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                Author and article information

                Journal
                Trends Cell Biol
                Trends Cell Biol
                Trends in Cell Biology
                Elsevier Science Publishers
                0962-8924
                1879-3088
                June 2010
                June 2010
                : 20
                : 6-3
                : 319-328
                Affiliations
                Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK
                Article
                TICB696
                10.1016/j.tcb.2010.03.005
                2927909
                20399659
                0c67d7bc-89d7-4413-bef5-58e25c894898
                © 2010 Elsevier Ltd.

                This document may be redistributed and reused, subject to certain conditions.

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                Cell biology
                Cell biology

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