Myosin IIA regulates cell motility and actomyosin-microtubule crosstalk. Nat Cell Biol.

Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health, Bethesda, MD 20892, USA.
Nature Cell Biology (Impact Factor: 20.06). 04/2007; 9(3):299-309. DOI: 10.1038/ncb1540
Source: PubMed

ABSTRACT Non-muscle myosin II has diverse functions in cell contractility, cytokinesis and locomotion, but the specific contributions of its different isoforms have yet to be clarified. Here, we report that ablation of the myosin IIA isoform results in pronounced defects in cellular contractility, focal adhesions, actin stress fibre organization and tail retraction. Nevertheless, myosin IIA-deficient cells display substantially increased cell migration and exaggerated membrane ruffling, which was dependent on the small G-protein Rac1, its activator Tiam1 and the microtubule moter kinesin Eg5. Myosin IIA deficiency stabilized microtubules, shifting the balance between actomyosin and microtubules with increased microtubules in active membrane ruffles. When microtubule polymerization was suppressed, myosin IIB could partially compensate for the absence of the IIA isoform in cellular contractility, but not in cell migration. We conclude that myosin IIA negatively regulates cell migration and suggest that it maintains a balance between the actomyosin and microtubule systems by regulating microtubule dynamics.

Download full-text


Available from: Sharona Even-Ram, Aug 25, 2015
  • Source
    • "Depletion of myosin IIA in carcinoma cell lines using siRNA decreased the number of stress fibers and focal adhesions and increased the rate of cell migration in a wound-healing assay [Sandquist et al., 2006]. Myosin IIA ablation in ES cells resulted in a marked decrease in contractility and an increase in cell migration velocity [Even-Ram et al., 2007]. RNAi experiments show that myosin IIA appears to function as the key negative regulator of cell spreading whereas myosin IIB depletion has little effect on spreading [Cai et al., 2006]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The actin cytoskeleton, which regulates cell polarity, adhesion, and migration, can influence cancer progression, including initial acquisition of malignant properties by normal cells, invasion of adjacent tissues, and metastasis to distant sites. Actin-dependent molecular motors, myosins, play key roles in regulating tumor progression and metastasis. In this review, we examine how non-muscle myosins regulate neoplastic transformation and cancer cell migration and invasion. Members of the myosin superfamily can act as either enhancers or suppressors of tumor progression. This review summarizes the current state of knowledge on how mutations or epigenetic changes in myosin genes and changes in myosin expression may affect tumor progression and patient outcomes and discusses the proposed mechanisms linking myosin inactivation or upregulation to malignant phenotype, cancer cell migration, and metastasis. © 2014 Wiley Periodicals, Inc.
    Cytoskeleton 08/2014; 71(8). DOI:10.1002/cm.21187 · 3.01 Impact Factor
  • Source
    • "Indeed, all known inhibitors of myosin II light chain phosphorylation, as well as the drug blebbistatin, which interferes with actin-dependent myosin II ATPase activity (Kovacs et al., 2004), were shown to prevent the formation of mature FAs, and induce rapid disassembly of existing ones (Geiger et al., 2009; Wolfenson et al., 2009a). The myosin IIA isoform was later shown to have a primary role in the growth and maintenance of FAs (Sandquist et al., 2006; Even-Ram et al., 2007; Vicente-Manzanares et al., 2007). The mechanosensory function of FAs was corroborated by experiments in which FA growth was induced by local mechanical stimulation (Riveline et al., 2001; Sniadecki et al., 2007). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Focal adhesions (FAs) have key roles in the interaction of cells with the extracellular matrix (ECM) and in adhesion-mediated signaling. These dynamic, multi-protein structures sense the ECM both chemically and physically, and respond to external and internal forces by changing their size and signaling activity. However, this mechanosensitivity is still poorly understood at the molecular level. Here, we present direct evidence that actomyosin contractility regulates the molecular kinetics of FAs. We show that the molecular turnover of proteins within FAs is primarily regulated by their dissociation rate constant (k(off)), which is sensitive to changes in forces applied to the FA. We measured the early changes in k(off) values for three FA proteins (vinculin, paxillin and zyxin) upon inhibition of actomyosin-generated forces using two methods - high temporal resolution FRAP and direct measurement of FA protein dissociation in permeabilized cells. When myosin II contractility was inhibited, the k(off) values for all three proteins changed rapidly, in a highly protein-specific manner: dissociation of vinculin from FAs was facilitated, whereas dissociation of paxillin and zyxin was attenuated. We hypothesize that these early kinetic changes initiate FA disassembly by affecting the molecular turnover of FAs and altering their composition.
    Journal of Cell Science 05/2011; 124(Pt 9):1425-32. DOI:10.1242/jcs.077388 · 5.33 Impact Factor
  • Source
    • "Myosin IIA may also represent an additional link between the actin cytoskeleton and microtubules. In other cell types, myosin IIA silencing increased microtubule stability in membrane protrusions [60]. It was also shown that microtubule movement requires a balanced action of myosin II and the microtubule-mediated motor dynein [61]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: T cell antigen receptor signaling is triggered and controlled in specialized cellular interfaces formed between T cells and antigen-presenting cells named immunological synapses. Both microtubules and actin cytoskeleton rearrange at the immunological synapse in response to T cell receptor triggering, ensuring in turn the accuracy of intracellular signaling. Recent reports show that the cross-talk between the cortical actin cytoskeleton and microtubule networks is key for structuring the immunological synapse and for controlling T cell receptor signaling. Immunological synapse architecture and the interaction between the signaling machinery and various cytoskeletal elements are therefore crucial for the fine-tuning of T cell signaling.
    FEBS letters 12/2010; 584(24):4845-50. DOI:10.1016/j.febslet.2010.09.001 · 3.34 Impact Factor
Show more