Abstract
Extracellular matrix (ECM) stiffness regulates cell differentiation, survival, and migration. Our previous study has shown that the interaction of the focal adhesion protein vinculin with vinexin α plays a critical role in sensing ECM stiffness and regulating stiffness-dependent cell migration. However, the mechanism how vinculin-vinexin α interaction affects stiffness-dependent cell migration is unclear. Lipid rafts are membrane microdomains that are known to affect ECM-induced signals and cell behaviors. Here, we show that vinculin and vinexin α can localize to lipid rafts. Cell-ECM adhesion, intracellular tension, and a rigid ECM promote vinculin distribution to lipid rafts. The disruption of lipid rafts with Methyl-β-cyclodextrin impaired the ECM stiffness-mediated regulation of vinculin behavior and rapid cell migration on rigid ECM. These results indicate that lipid rafts play an important role in ECM-stiffness regulation of cell migration via vinculin.
Keywords:
extracellular matrix; focal adhesions; lipid raft; mechanotransduction; vinculin.
MeSH terms
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Animals
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Biomechanical Phenomena
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Caveolin 1 / genetics
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Caveolin 1 / metabolism
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Cell Adhesion / drug effects
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Cell Line
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Cell Movement / drug effects
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Embryo, Mammalian
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Extracellular Matrix / drug effects
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Extracellular Matrix / metabolism*
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Extracellular Matrix / ultrastructure
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Fibroblasts / drug effects
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Fibroblasts / metabolism*
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Fibroblasts / ultrastructure
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Focal Adhesions / drug effects
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Focal Adhesions / metabolism*
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Focal Adhesions / ultrastructure
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Gene Expression Regulation
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Hardness
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Membrane Microdomains / drug effects
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Membrane Microdomains / metabolism*
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Membrane Microdomains / ultrastructure
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mice
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Muscle Proteins / genetics
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Muscle Proteins / metabolism*
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Paxillin / genetics
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Paxillin / metabolism
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Protein Binding
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Signal Transduction
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Vinculin / genetics
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Vinculin / metabolism*
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beta-Cyclodextrins / pharmacology
Substances
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Caveolin 1
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Membrane Proteins
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Muscle Proteins
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Paxillin
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Protein Isoforms
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Pxn protein, mouse
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Sorbs3 protein, mouse
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beta-Cyclodextrins
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flotillins
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methyl-beta-cyclodextrin
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Vinculin