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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.

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Available from: Sharona Even-Ram, Aug 25, 2015
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    • "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]. "
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    • "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). "
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    • "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]. "
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