Non-muscle myosin II takes centre stage in cell adhesion and migration.
01 Nov 2009-Nature Reviews Molecular Cell Biology (Nature Publishing Group)-Vol. 10, Iss: 11, pp 778-790
TL;DR: Non-muscle myosin II is an actin-binding protein that has actin cross-linking and contractile properties and is regulated by the phosphorylation of its light and heavy chains.
Abstract: Non-muscle myosin II (NM II) is an actin-binding protein that has actin cross-linking and contractile properties and is regulated by the phosphorylation of its light and heavy chains. The three mammalian NM II isoforms have both overlapping and unique properties. Owing to its position downstream of convergent signalling pathways, NM II is central in the control of cell adhesion, cell migration and tissue architecture. Recent insight into the role of NM II in these processes has been gained from loss-of-function and mutant approaches, methods that quantitatively measure actin and adhesion dynamics and the discovery of NM II mutations that cause monogenic diseases.
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TL;DR: Adhesion formation and disassembly drive the migration cycle by activating Rho GTPases, which in turn regulate actin polymerization and myosin II activity, and therefore adhesion dynamics.
Abstract: Cell migration affects all morphogenetic processes and contributes to numerous diseases, including cancer and cardiovascular disease. For most cells in most environments, movement begins with protrusion of the cell membrane followed by the formation of new adhesions at the cell front that link the actin cytoskeleton to the substratum, generation of traction forces that move the cell forwards and disassembly of adhesions at the cell rear. Adhesion formation and disassembly drive the migration cycle by activating Rho GTPases, which in turn regulate actin polymerization and myosin II activity, and therefore adhesion dynamics.
1,775Â citations
Cites background from "Non-muscle myosin II takes centre s..."
...Myosin II also bundles actin filaments owing to its oligomeric nature and actin-binding propertie...
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Abstract: Actin filaments assemble into diverse protrusive and contractile structures to provide force for a number of vital cellular processes. Stress fibers are contractile actomyosin bundles found in many cultured non-muscle cells, where they have a central role in cell adhesion and morphogenesis. Focal-adhesion-anchored stress fibers also have an important role in mechanotransduction. In animal tissues, stress fibers are especially abundant in endothelial cells, myofibroblasts and epithelial cells. Importantly, recent live-cell imaging studies have provided new information regarding the mechanisms of stress fiber assembly and how their contractility is regulated in cells. In addition, these studies might elucidate the general mechanisms by which contractile actomyosin arrays, including muscle cell myofibrils and cytokinetic contractile ring, can be generated in cells. In this Commentary, we discuss recent findings concerning the physiological roles of stress fibers and the mechanism by which these structures are generated in cells.
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TL;DR: This review summarizes current knowledge on the structural organization, composition, and mechanics of the actin cortex, focusing on the link between molecular processes and macroscopic physical properties and consequences of cortex dysfunction in disease.
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TL;DR: In this paper, integrin-based adhesion has been studied as a model for studying the central role of adhesion in migration and the authors outline modes of migration, both integrindependent and independent in vitro and in vivo.
Abstract: Integrin-based adhesion has served as a model for studying the central role of adhesion in migration. In this article, we outline modes of migration, both integrin-dependent and -independent in vitro and in vivo. We next discuss the roles of adhesion contacts as signaling centers and linkages between the ECM and actin that allows adhesions to serve as traction sites. This includes signaling complexes that regulate migration and the interplay among adhesion, signaling, and pliability of the substratum. Finally, we address mechanisms of adhesion assembly and disassembly and the role of adhesion in cellular polarity.
694Â citations
Cites background from "Non-muscle myosin II takes centre s..."
...Rac/Cdc42 may also regulate myosin activity through PAK by inhibiting MLCK or phosphorylating RLC directly (Vicente-Manzanares et al. 2009)....
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...…subclasses can now be identified, e.g., nascent adhesions, focal complexes, focal adhesions, and fibrillar adhesions (Zaidel-Bar et al. 2004; Vicente-Manzanares et al. 2009; Geiger and Yamada 2011), the last of which will not be discussed here because they are not typically present in…...
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...feedback loop connects adhesion, contraction, and pliability (Vicente-Manzanares et al. 2009)....
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...4 Cite this article as Cold Spring Harb Perspect Biol 2011;3:a005074 feedback loop connects adhesion, contraction, and pliability (Vicente-Manzanares et al. 2009)....
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..., nascent adhesions, focal complexes, focal adhesions, and fibrillar adhesions (Zaidel-Bar et al. 2004; Vicente-Manzanares et al. 2009; Geiger and Yamada 2011), the last of which will not be discussed here because they are not typically present in migrating cells....
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TL;DR: The recent studies have described how leader cells at the front of cell groups drive migration and have highlighted the importance of follower cells and cell-cell communication, both between followers and between follower and leader cells, to improve the efficiency of collective movement.
Abstract: Collective cell migration has a key role during morphogenesis and during wound healing and tissue renewal in the adult, and it is involved in cancer spreading. In addition to displaying a coordinated migratory behaviour, collectively migrating cells move more efficiently than if they migrated separately, which indicates that a cellular interplay occurs during collective cell migration. In recent years, evidence has accumulated confirming the importance of such intercellular communication and exploring the molecular mechanisms involved. These mechanisms are based both on direct physical interactions, which coordinate the cellular responses, and on the collective cell behaviour that generates an optimal environment for efficient directed migration. The recent studies have described how leader cells at the front of cell groups drive migration and have highlighted the importance of follower cells and cell-cell communication, both between followers and between follower and leader cells, to improve the efficiency of collective movement.
641Â citations
References
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TL;DR: The mechanisms underlying the major steps of migration and the signaling pathways that regulate them are described, and recent advances investigating the nature of polarity in migrating cells and the pathways that establish it are outlined.
Abstract: Cell migration is a highly integrated multistep process that orchestrates embryonic morphogenesis; contributes to tissue repair and regeneration; and drives disease progression in cancer, mental retardation, atherosclerosis, and arthritis. The migrating cell is highly polarized with complex regulatory pathways that spatially and temporally integrate its component processes. This review describes the mechanisms underlying the major steps of migration and the signaling pathways that regulate them, and outlines recent advances investigating the nature of polarity in migrating cells and the pathways that establish it.
4,839Â citations
"Non-muscle myosin II takes centre s..." refers background in this paper
...The molecular composition and organization of these front and rear compartments is distinc...
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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.
3,793Â citations
TL;DR: The mechanisms of such environmental sensing are discussed, based on the finely tuned crosstalk between the assembly of one type of integrin-based adhesion complex, namely focal adhesions, and the forces that are at work in the associated cytoskeletal network owing to actin polymerization and actomyosin contraction.
Abstract: Recent progress in the design and application of artificial cellular microenvironments and nanoenvironments has revealed the extraordinary ability of cells to adjust their cytoskeletal organization, and hence their shape and motility, to minute changes in their immediate surroundings. Integrin-based adhesion complexes, which are tightly associated with the actin cytoskeleton, comprise the cellular machinery that recognizes not only the biochemical diversity of the extracellular neighbourhood, but also its physical and topographical characteristics, such as pliability, dimensionality and ligand spacing. Here, we discuss the mechanisms of such environmental sensing, based on the finely tuned crosstalk between the assembly of one type of integrin-based adhesion complex, namely focal adhesions, and the forces that are at work in the associated cytoskeletal network owing to actin polymerization and actomyosin contraction.
2,322Â citations
"Non-muscle myosin II takes centre s..." refers background in this paper
...Other signalling pathways activated by adhesion have the opposite effect and promote NM II activation through RHO...
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TL;DR: It is suggested that the RhoA/ROK pathway is constitutively active in a number of organs under physiological conditions; its aberrations play major roles in several disease states, particularly impacting on Ca2+ sensitization of smooth muscle in hypertension and possibly asthma and on cancer neoangiogenesis and cancer progression.
Abstract: Somlyo, Andrew P., and Avril V. Somlyo. Ca2+ Sensitivity of Smooth Muscle and Nonmuscle Myosin II: Modulated by G Proteins, Kinases, and Myosin Phosphatase. Physiol Rev 83: 1325-1358, 2003; 10.1152...
1,923Â citations
TL;DR: It is demonstrated that stimulation of fibroblasts with lysophosphatidic acid, which activates rho, induces myosin light chain phosphorylation, which precedes the formation of stress fibers and focal adhesions and is accompanied by increased contractility.
Abstract: Activated rhoA, a ras-related GTP-binding protein, stimulates the appearance of stress fibers, focal adhesions, and tyrosine phosphorylation in quiescent cells (Ridley, A.J., and A. Hall, 1992. Cell. 70:389-399). The pathway by which rho triggers these events has not been elucidated. Many of the agents that activate rho (e.g., vasopressin, endothelin, lysophosphatidic acid) stimulate the contractility of smooth muscle and other cells. We have investigated whether rho's induction of stress fibers, focal adhesions, and tyrosine phosphorylation is the result of its stimulation of contractility. We demonstrate that stimulation of fibroblasts with lysophosphatidic acid, which activates rho, induces myosin light chain phosphorylation. This precedes the formation of stress fibers and focal adhesions and is accompanied by increased contractility. Inhibition of contractility by several different mechanisms leads to inhibition of rho-induced stress fibers, focal adhesions, and tyrosine phosphorylation. In addition, when contractility is inhibited, integrins disperse from focal adhesions as stress fibers and focal adhesions disassemble. Conversely, upon stimulation of contractility, diffusely distributed integrins are aggregated into focal adhesions. These results suggest that activated rho stimulates contractility, driving the formation of stress fibers and focal adhesions and elevating tyrosine phosphorylation. A model is proposed to account for how contractility could promote these events.
1,707Â citations
"Non-muscle myosin II takes centre s..." refers background in this paper
...NM IIA specifically mediates retraction of the trailing edge during migratio...
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