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.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Actomyosin / metabolism*
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Aminoquinolines / pharmacology
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Animals
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Azepines / pharmacology
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COS Cells
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Cell Adhesion / physiology
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Cell Movement / drug effects
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Cell Movement / physiology*
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Chlorocebus aethiops
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Embryonic Stem Cells / cytology
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Embryonic Stem Cells / drug effects
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Embryonic Stem Cells / metabolism
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Enzyme Inhibitors / pharmacology
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Fibroblasts / cytology
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Fibroblasts / drug effects
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Fibroblasts / metabolism
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Guanine Nucleotide Exchange Factors / genetics
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Guanine Nucleotide Exchange Factors / metabolism
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Heterocyclic Compounds, 4 or More Rings / pharmacology
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Humans
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Kinesins / antagonists & inhibitors
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Kinesins / genetics
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Kinesins / metabolism
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Mice
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Microtubules / drug effects
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Microtubules / metabolism*
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Naphthalenes / pharmacology
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Nocodazole / pharmacology
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Nonmuscle Myosin Type IIA / antagonists & inhibitors
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Nonmuscle Myosin Type IIA / genetics
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Nonmuscle Myosin Type IIA / physiology*
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Nonmuscle Myosin Type IIB / antagonists & inhibitors
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Nonmuscle Myosin Type IIB / genetics
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Nonmuscle Myosin Type IIB / physiology
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Pyrimidines / pharmacology
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RNA, Small Interfering / genetics
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T-Lymphoma Invasion and Metastasis-inducing Protein 1
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Thiones / pharmacology
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Transfection
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Vinblastine / pharmacology
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rac1 GTP-Binding Protein / antagonists & inhibitors
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rac1 GTP-Binding Protein / genetics
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rac1 GTP-Binding Protein / metabolism
Substances
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Aminoquinolines
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Azepines
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Enzyme Inhibitors
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Guanine Nucleotide Exchange Factors
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Heterocyclic Compounds, 4 or More Rings
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KIF11 protein, human
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NSC 23766
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Naphthalenes
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Pyrimidines
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RNA, Small Interfering
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T-Lymphoma Invasion and Metastasis-inducing Protein 1
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Thiones
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Tiam1 protein, mouse
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ML 7
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blebbistatin
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Vinblastine
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monastrol
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Actomyosin
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Nonmuscle Myosin Type IIA
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Nonmuscle Myosin Type IIB
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Kinesins
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rac1 GTP-Binding Protein
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Nocodazole