Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration.
Rho family GTPases, particularly Rac1 and Cdc42, are key regulators of cell polarization and directional migration. Adenomatous polyposis coli (APC) is also thought to play a pivotal role in polarized cell migration. We have found that IQGAP1, an effector of Rac1 and Cdc42, interacts directly with APC. IQGAP1 and APC localize interdependently to the leading edge in migrating Vero cells, and activated Rac1/Cdc42 form a ternary complex with IQGAP1 and APC. Depletion of either IQGAP1 or APC inhibits actin meshwork formation and polarized migration. Depletion of IQGAP1 or APC also disrupts localization of CLIP-170, a microtubule-stabilizing protein that interacts with IQGAP1. Taken together, these results suggest a model in which activation of Rac1 and Cdc42 in response to migration signals leads to recruitment of IQGAP1 and APC which, together with CLIP-170, form a complex that links the actin cytoskeleton and microtubule dynamics during cell polarization and directional migration.
Watanabe
Takashi
T
Department of Cell Pharmacology, Nagoya University, Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi 466-8550, Japan.
Wang
Shujie
S
Noritake
Jun
J
Sato
Kazumasa
K
Fukata
Masaki
M
Takefuji
Mikito
M
Nakagawa
Masato
M
Izumi
Nanae
N
Akiyama
Tetsu
T
Kaibuchi
Kozo
K
D000199:Actins / Q000378:metabolism; D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002465:Cell Movement; D002522:Chlorocebus aethiops; D005347:Fibroblasts / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D047468:Immunoprecipitation; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D009363:Neoplasm Proteins; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D014709:Vero Cells; D014945:Wound Healing; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins / Q000502:physiology*
D000199:Actins; D025601:Adenomatous Polyposis Coli Protein; C101203:IQ motif containing GTPase activating protein 1; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D020703:ras GTPase-Activating Proteins; D049452:Green Fluorescent Proteins; C076744:cytoplasmic linker protein 170; D005982:Glutathione Transferase; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein