Abstract
We describe here a signal transduction pathway controlling the establishment of mammalian cell polarity. Scratching a confluent monolayer of primary rat astrocytes leads to polarization of cells at the leading edge. The microtubule organizing center, the microtubule cytoskeleton, and the Golgi reorganize to face the new free space, and directed cell protrusion and migration specifically occur perpendicularly to the scratch. We show here that the interaction of integrins with extracellular matrix at the newly formed cell front leads to the activation and polarized recruitment of Cdc42, which in turn recruits and activates a cytoplasmic mPar6/PKCzeta complex. Localized PKCzeta activity, acting through the microtubule motor protein dynein, is required for all aspects of induced polarity in these cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology
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Astrocytes / cytology
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Astrocytes / drug effects
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Astrocytes / physiology*
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COS Cells
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Cell Movement / physiology
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Cell Polarity*
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Cells, Cultured
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Dyneins / metabolism
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Enzyme Inhibitors / pharmacology
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Genes, Reporter
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Golgi Apparatus / metabolism
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Immunoblotting
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Integrins / metabolism*
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Microtubule-Organizing Center / metabolism
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Oligopeptides / pharmacology
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Protein Kinase C / metabolism*
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Rats
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Signal Transduction / physiology*
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Wound Healing / physiology
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cdc42 GTP-Binding Protein / genetics
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cdc42 GTP-Binding Protein / metabolism*
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rac GTP-Binding Proteins / genetics
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rac GTP-Binding Proteins / metabolism
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rho GTP-Binding Proteins / genetics
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rho GTP-Binding Proteins / metabolism
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Integrins
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Oligopeptides
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Recombinant Fusion Proteins
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arginyl-glycyl-aspartic acid
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protein kinase C zeta
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Protein Kinase C
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Dyneins
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cdc42 GTP-Binding Protein
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rac GTP-Binding Proteins
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rho GTP-Binding Proteins