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Myosin IIA regulates cell motility and actomyosin–microtubule crosstalk

An Addendum to this article was published on 01 April 2007

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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Figure 1: The steady-state balance between myosin IIA and microtubules is altered after in vitro wounding.
Figure 2: Genetic myosin IIA deficiency impairs formation of actin stress fibres and focal adhesions.
Figure 3: Myosin IIA depletion impairs contractility but increases migration rates.
Figure 4: Rac activation in myosin IIA-deficient cells.
Figure 5: Microtubule expansion in myosin IIA-deficient cells.
Figure 6: Disruption of microtubules restores contractility of myosin IIA-deficient cells.
Figure 7: Inhibition of Eg5 kinesin abolishes the increase in migration and membrane ruffling of myosin II-deficient cells.

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Acknowledgements

This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Dental and Craniofacial Research and National Heart, Lung, and Blood Institute.

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Correspondence to Kenneth M. Yamada.

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Even-Ram, S., Doyle, A., Conti, M. et al. Myosin IIA regulates cell motility and actomyosin–microtubule crosstalk. Nat Cell Biol 9, 299–309 (2007). https://doi.org/10.1038/ncb1540

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