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Cited by 480Protein Kinase Regulation and GTPase SignalingCellular Mechanics and InteractionsAxon Guidance and Neuronal Signaling

Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration

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Watanabe, Takashi, Wang, Shujie, Noritake, Jun, Sato, Kazumasa, Fukata, Masaki, Takefuji, Mikito, Nakagawa, Masato, Izumi, Nanae +2 more·2004·Developmental Cell
DOI 10.1016/j.devcel.2004.10.017
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Abstract

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.

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Cited by

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Authors
Watanabe, T., Wang, S., Noritake, J., Sato, K., Fukata, M., Takefuji, M., Nakagawa, M., Izumi, N., Akiyama, T., & Kaibuchi, K.
Affiliations
  • Nagoya University (JP)
  • The University of Tokyo (JP)
Corresponding author
Kaibuchi, Kozo
ORCID
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2004-12
Volume
7
Issue
6
Pages
871-883
ISSN
1534-5807 (ISSN-L)
DOI
10.1016/j.devcel.2004.10.017
OpenAlex
W2018516624
Cited by
480
References
0
Citations by year
2026: 3 · 2025: 9 · 2024: 6 · 2023: 12 · 2022: 11 · 2021: 21 · 2020: 15 · 2019: 19 · 2018: 20 · 2017: 21 · 2016: 23 · 2015: 23 · 2014: 31 · 2013: 25 · 2012: 26
FWCI
10.68
Type
journal article
Language
en
Open access
Licence
Locations
  • Developmental Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
Ministry of Education, Culture, Sports, Science and Technology
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
Keywords
IQGAP1, APC, Rac1, Cdc42, Rho GTPases, cell polarization, directional cell migration, actin cytoskeleton, microtubules, CLIP-170, leading edge, ternary complex, Vero cells
MeSH terms
Actins, Animals, Binding Sites, Cell Movement, Chlorocebus aethiops, Fibroblasts, Glutathione Transferase, Image Processing, Computer-Assisted, Microscopy, Fluorescence, Microtubule-Associated Proteins, Microtubules, Models, Biological, Neoplasm Proteins, Plasmids, Protein Binding, Recombinant Fusion Proteins, Time Factors, Transfection, Vero Cells, Wound Healing, Signal Transduction, COS Cells, ras GTPase-Activating Proteins, cdc42 GTP-Binding Protein, rac1 GTP-Binding Protein, Adenomatous Polyposis Coli Protein, RNA, Small Interfering, Immunoprecipitation, Green Fluorescent Proteins

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