TY - JOUR
T1 - Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration
AU - Watanabe, Takashi
AU - Wang, Shujie
AU - Noritake, Jun
AU - Sato, Kazumasa
AU - Fukata, Masaki
AU - Takefuji, Mikito
AU - Nakagawa, Masato
AU - Izumi, Nanae
AU - Akiyama, Tetsu
AU - Kaibuchi, Kozo
N1 - Funding Information:
We thank Dr. I.S. Näthke (University of Dundee) for providing anti-APC antibody, Dr. F. Perez (Curie Institute) for providing CLIP-170 cDNA, Dr. E. Mekada (Osaka University) for providing Vero cells, and Dr. A. Kikuchi (Hiroshima University) for providing some APC constructs. We also thank Dr. Y. Fukata (Nagoya University), Dr. Y. Kawasaki (Tokyo University), and Dr. H. Saya (Kumamoto University) for helpful discussion and preparing some materials, and T. Ishii, S. Kamisawa, and S. Kozawa for secretarial and technical assistance. This research was supported in part by Grants-in-Aid for Scientific Research, a Grant-in-Aid for Creative Scientific Research, and The 21st Century Centre of Excellence (COE) Program from MEXT, SCFPST, PMDA, and The Nitto Foundation.
PY - 2004/12
Y1 - 2004/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/10644281068
UR - https://www.scopus.com/pages/publications/10644281068#tab=citedBy
U2 - 10.1016/j.devcel.2004.10.017
DO - 10.1016/j.devcel.2004.10.017
M3 - Article
C2 - 15572129
AN - SCOPUS:10644281068
SN - 1534-5807
VL - 7
SP - 871
EP - 883
JO - Developmental Cell
JF - Developmental Cell
IS - 6
ER -