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      Actomyosin contractility and collective migration: may the force be with you

      review-article
      , ,
      Current Opinion in Cell Biology
      Elsevier

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          Highlights

          • Collective migration relies on the ability of a multicellular co-ordinated unit to efficiently respond to physical changes in their surrounding matrix.

          • Conversely, migrating cohorts physically alter their microenvironment using mechanical forces.

          • During collective migration, actomyosin contractility acts as a central hub coordinating mechanosensing and mechanotransduction responses.

          Abstract

          Collective cell migration is essential during physiological processes such as development or wound healing and in pathological conditions such as cancer dissemination. Cells migrating within multicellular tissues experiment different forces which play an intricate role during tissue formation, development and maintenance. How cells are able to respond to these forces depends largely on how they interact with the extracellular matrix. In this review, we focus on mechanics and mechanotransduction in collective migration. In particular, we discuss current knowledge on how cells integrate mechanical signals during collective migration and we highlight actomyosin contractility as a central hub coordinating mechanosensing and mechanotransduction responses.

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          Most cited references62

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          Endothelial cell migration during angiogenesis.

          Endothelial cell migration is essential to angiogenesis. This motile process is directionally regulated by chemotactic, haptotactic, and mechanotactic stimuli and further involves degradation of the extracellular matrix to enable progression of the migrating cells. It requires the activation of several signaling pathways that converge on cytoskeletal remodeling. Then, it follows a series of events in which the endothelial cells extend, contract, and throw their rear toward the front and progress forward. The aim of this review is to give an integrative view of the signaling mechanisms that govern endothelial cell migration in the context of angiogenesis.
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            Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase).

            The small GTPase Rho is implicated in physiological functions associated with actin-myosin filaments such as cytokinesis, cell motility, and smooth muscle contraction. We have recently identified and molecularly cloned Rho-associated serine/threonine kinase (Rho-kinase), which is activated by GTP Rho (Matsui, T., Amano, M., Yamamoto, T., Chihara, K., Nakafuku, M., Ito, M., Nakano, T., Okawa, K., Iwamatsu, A., and Kaibuchi, K. (1996) EMBO J. 15, 2208-2216). Here we found that Rho-kinase stoichiometrically phosphorylated myosin light chain (MLC). Peptide mapping and phosphoamino acid analyses revealed that the primary phosphorylation site of MLC by Rho-kinase was Ser-19, which is the site phosphorylated by MLC kinase. Rho-kinase phosphorylated recombinant MLC, whereas it failed to phosphorylate recombinant MLC, which contained Ala substituted for both Thr-18 and Ser-19. We also found that the phosphorylation of MLC by Rho-kinase resulted in the facilitation of the actin activation of myosin ATPase. Thus, it is likely that once Rho is activated, then it can interact with Rho-kinase and activate it. The activated Rho-kinase subsequently phosphorylates MLC. This may partly account for the mechanism by which Rho regulates cytokinesis, cell motility, or smooth muscle contraction.
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              Integrin structure, activation, and interactions.

              Integrins are large, membrane-spanning, heterodimeric proteins that are essential for a metazoan existence. All members of the integrin family adopt a shape that resembles a large "head" on two "legs," with the head containing the sites for ligand binding and subunit association. Most of the receptor dimer is extracellular, but both subunits traverse the plasma membrane and terminate in short cytoplasmic domains. These domains initiate the assembly of large signaling complexes and thereby bridge the extracellular matrix to the intracellular cytoskeleton. To allow cells to sample and respond to a dynamic pericellular environment, integrins have evolved a highly responsive receptor activation mechanism that is regulated primarily by changes in tertiary and quaternary structure. This review summarizes recent progress in the structural and molecular functional studies of this important class of adhesion receptor.
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                Author and article information

                Contributors
                Journal
                Curr Opin Cell Biol
                Curr. Opin. Cell Biol
                Current Opinion in Cell Biology
                Elsevier
                0955-0674
                1879-0410
                1 October 2017
                October 2017
                : 48
                : 87-96
                Affiliations
                [0005]Tumour Plasticity Team, Randall Division of Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, King's College London, London SE1 1UL, UK
                Article
                S0955-0674(17)30026-1
                10.1016/j.ceb.2017.06.006
                6137077
                28715714
                a6fb7c11-3f7e-44c3-bba9-4c1c82e577a5
                © 2017 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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                Cell biology
                Cell biology

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