Cdc42 controls the polarity of the actin and microtubule cytoskeletons through two distinct signal transduction pathways.
Cdc42, a Rho family GTPase, is a key regulator of cell polarity. In Saccharomyces cerevisiae, it is required for polarized bud formation and pheromone gradient sensing, while in higher eukaryotes, it participates in asymmetric cell division, directional sensing during migration, and morphogenesis. Using a scratch-induced fibroblast migration assay, we previously showed that Cdc42 controls the polarization of both membrane protrusions and the Golgi/centrosome. We now find that Golgi/centrosome polarity is mediated through activation of the Par6/aPKC complex, as previously described in astrocytes. However, this complex is not involved in Cdc42-dependent polarization of protrusions, which instead is mediated by Pak acting through the Rac guanine nucleotide exchange factor, betaPIX. Pak kinase activity is essential for spatially restricting Rac-dependent actin polymerization to the leading edge of the migrating cells, though it is not required for actin polymerization per se. We conclude that in migrating cells, Cdc42 co-ordinately regulates the polarity of the microtubule and actin cytoskeletons through two distinct pathways.
Cau
Julien
J
MRC Laboratory for Molecular Cell Biology, Cancer Research UK Oncogene and Signal Transduction Group, University College London.
Hall
Alan
A
D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism; D016764:Cell Polarity; D022081:Cell Surface Extensions / Q000378:metabolism; D002478:Cells, Cultured; D006056:Golgi Apparatus / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction; D015854:Up-Regulation / Q000235:genetics; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; C504908:Pard6a protein, rat; D064067:Rho Guanine Nucleotide Exchange Factors; C515906:Pak1 protein, rat; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; C115015:PKC-3 protein; D011493:Protein Kinase C; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins