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Review
. 2015 Oct:36:103-12.
doi: 10.1016/j.ceb.2015.08.005. Epub 2015 Sep 10.

Rho GTPase signalling in cell migration

Anne J Ridley  1
Affiliations
Review

Rho GTPase signalling in cell migration

Anne J Ridley. Curr Opin Cell Biol. 2015 Oct.

Abstract

Cells migrate in multiple different ways depending on their environment, which includes the extracellular matrix composition, interactions with other cells, and chemical stimuli. For all types of cell migration, Rho GTPases play a central role, although the relative contribution of each Rho GTPase depends on the environment and cell type. Here, I review recent advances in our understanding of how Rho GTPases contribute to different types of migration, comparing lamellipodium-driven versus bleb-driven migration modes. I also describe how cells migrate across the endothelium. In addition to Rho, Rac and Cdc42, which are well known to regulate migration, I discuss the roles of other less-well characterized members of the Rho family.

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Figures

Figure 1
Figure 1
Rho GTPases in lamellipodium-driven migration. In cells using lamellipodia to drive migration, cell migratory polarity is established by Cdc42, acting through the Par polarity complex and microtubules. Membrane protrusions at the front of cells include lamellipodia and filopodia. Cdc42 is the main GTPase contributing to filopodium extension, acting through mDia formins. Rac induces lamellipodium extension through the WAVE complex, which activates the Arp2/3 complex. Adhesions to the extracellular matrix form in lamellipodia, initially through Rac and its target PAK, among other proteins. Rho and ROCKs promote formation of larger, more persistent integrin-based adhesions. Actomyosin contraction in the cell body is important for driving the cell forward and for detachment of the back of the cell, and is mediated by Rho and ROCKs and/or Cdc42 and MRCKs.
Figure 2
Figure 2
Signalling in lamellipodia. In lamellipodium-driven migration, actin polymerization at the front of cells requires Rac, which recruits the WAVE complex to activate Arp2/3 complex-mediated actin polymerization. VASP and the adaptor protein lamellipodin (which interacts with VASP, Rac and the WAVE complex) contribute to actin polymerization. RhoA is also active at the front of extending lamellipodia, and might contribute to actin polymerization through a formin such as mDia1. Cdc42 and integrins contribute to inducing and maintaining active Rac selectively at the leading edge of migrating cells. Negative feedback loops restrict the extent of Rac activation, including Arpin (which inhibits the Arp2/3 complex) and SrGAP1 (a GAP for Rac). RhoC acts further back in the cell, behind Rac, to downregulate cofilin activity (via LIMK) and hence decrease actin polymerization, and stimulate actomyosin contractility (via ROCK), which pulls the lamellipodial network rearwards. During migration, integrin-based focal contacts need to be turned over, and this involves Rac itself, acting through a PAK/GIT/β-PIX complex that is localized to focal contacts. RhoJ and RhoD also contribute to focal contact turnover.
Figure 3
Figure 3
Rho GTPases in bleb-driven migration. The predominant Rho GTPase involved in bleb-driven migration is RhoA, acting through ROCK to stimulate myosin light chain phosphorylation (pMLC) and hence cortical actomyosin contractility, which is higher at the front and back of the cell than on the sides. At the back of the cell, ezrin is associated with the actin cortex and reduces bleb formation [111]. At the front of the cell, actomyosin contractility leads to focal detachment of the plasma membrane from the actin cortex to form blebs, which initially do not contain actin filaments (shown in blue). Subsequently actin polymerizes on the bleb membrane to stabilize the protrusion, eventually leading to bleb retraction. This could be mediated by Rac, which as activated at the front of blebbing primordial germ cells in zebrafish by the G-protein subunits Gβγ.
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References

    1. Mayor R., Theveneau E. The neural crest. Development. 2013;140:2247–2251. - PubMed
    1. Spano D., Heck C., De Antonellis P., Christofori G., Zollo M. Molecular networks that regulate cancer metastasis. Semin Cancer Biol. 2012;22:234–249. - PubMed
    1. Griffith J.W., Luster A.D. Targeting cells in motion: migrating toward improved therapies. Eur J Immunol. 2013;43:1430–1435. - PMC - PubMed
    1. Friedl P., Locker J., Sahai E., Segall J.E. Classifying collective cancer cell invasion. Nat Cell Biol. 2012;14:777–783. - PubMed
    1. Paluch E.K., Raz E. The role and regulation of blebs in cell migration. Curr Opin Cell Biol. 2013;25:582–590. - PMC - PubMed

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