Integrin-mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCzeta.
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.
Etienne-Manneville
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MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, WC1E 6BT, London, United Kingdom.
Hall
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D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D019556:COS Cells; D002465:Cell Movement / Q000502:physiology; D016764:Cell Polarity; D002478:Cells, Cultured; D004398:Dyneins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017930:Genes, Reporter; D006056:Golgi Apparatus / Q000378:metabolism; D015151:Immunoblotting; D016023:Integrins / Q000378:metabolism*; D022101:Microtubule-Organizing Center / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000099221:Protein Kinase C zeta
D000970:Antineoplastic Agents; D004398:Dyneins; D004791:Enzyme Inhibitors; D016023:Integrins; D009842:Oligopeptides; D011493:Protein Kinase C; D011993:Recombinant Fusion Proteins; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D000099221:Protein Kinase C zeta; C047981:arginyl-glycyl-aspartic acid