Cdc42 and Par6-PKCzeta regulate the spatially localized association of Dlg1 and APC to control cell polarization.
Cell polarization is essential in a wide range of biological processes such as morphogenesis, asymmetric division, and directed migration. In this study, we show that two tumor suppressor proteins, adenomatous polyposis coli (APC) and Dlg1-SAP97, are required for the polarization of migrating astrocytes. Activation of the Par6-PKCzeta complex by Cdc42 at the leading edge of migrating cells promotes both the localized association of APC with microtubule plus ends and the assembly of Dlg-containing puncta in the plasma membrane. Biochemical analysis and total internal reflection fluorescence microscopy reveal that the subsequent physical interaction between APC and Dlg1 is required for polarization of the microtubule cytoskeleton.
Etienne-Manneville
Sandrine
S
Medical Research Council Laboratory for Molecular Cell Biology, University College London, London WC1E 68T, UK.
Manneville
Jean-Baptiste
JB
Nicholls
Sarah
S
Ferenczi
Michael A
MA
Hall
Alan
A
D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D016764:Cell Polarity; D002478:Cells, Cultured; D004789:Enzyme Activation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D011493:Protein Kinase C / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D002352:Carrier Proteins; C499657:PARD6A protein, human; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D000429:Alcohol Oxidoreductases; C082646:leukotriene B4 12-hydroxydehydrogenase; D000071679:Glycogen Synthase Kinase 3 beta; D011493:Protein Kinase C; D038362:Glycogen Synthase Kinase 3; D020764:cdc42 GTP-Binding Protein