Cdc42 and noncanonical Wnt signal transduction pathways cooperate to promote cell polarity.
Scratch-induced disruption of cultured monolayers induces polarity in front row cells that can be visualized by spatially localized polymerization of actin at the front of the cell and reorientation of the centrosome/Golgi to face the leading edge. We previously reported that centrosomal reorientation and microtubule polarization depend on a Cdc42-regulated signal transduction pathway involving activation of the Par6/aPKC complex followed by inhibition of GSK-3beta and accumulation of the adenomatous polyposis coli (APC) protein at the plus ends of leading-edge microtubules. Using monolayers of primary rodent embryo fibroblasts, we show here that dishevelled (Dvl) and axin, two major components of the Wnt signaling pathway are required for centrosome reorientation and that Wnt5a is required for activation of this pathway. We conclude that disruption of cell-cell contacts leads to the activation of a noncanonical Wnt/dishevelled signal transduction pathway that cooperates with Cdc42/Par6/aPKC to promote polarized reorganization of the microtubule cytoskeleton.
Schlessinger
Karni
K
Medical Research Council Laboratory for Molecular Cell Biology, Cancer Research UK Oncogene and Signal Transduction Group and Department of Biochemistry and Molecular Biology, University College London, London, England, UK.
McManus
Edward J
EJ
Hall
Alan
A
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000818:Animals; D060466:Axin Protein; D002450:Cell Communication / Q000502:physiology; D016764:Cell Polarity; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D000072261:Dishevelled Proteins; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D060466:Axin Protein; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D051153:Wnt Proteins; C115015:PKC-3 protein; D011493:Protein Kinase C; D038362:Glycogen Synthase Kinase 3; D020764:cdc42 GTP-Binding Protein