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

Takashi Watanabe; Shujie Wang; Jun Noritake; Kazumasa Sato; Masaki Fukata; Mikito Takefuji; Masato Nakagawa; Nanae Izumi; Tetsu Akiyama; Kozo Kaibuchi

doi:10.1016/j.devcel.2004.10.017

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

Dev Cell. 2004 Dec;7(6):871-83. doi: 10.1016/j.devcel.2004.10.017.

Authors

Takashi Watanabe¹, Shujie Wang, Jun Noritake, Kazumasa Sato, Masaki Fukata, Mikito Takefuji, Masato Nakagawa, Nanae Izumi, Tetsu Akiyama, Kozo Kaibuchi

Affiliation

¹ Department of Cell Pharmacology, Nagoya University, Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi 466-8550, Japan.

PMID: 15572129
DOI: 10.1016/j.devcel.2004.10.017

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actins / metabolism
Adenomatous Polyposis Coli Protein / metabolism*
Animals
Binding Sites
COS Cells
Cell Movement
Chlorocebus aethiops
Fibroblasts / metabolism
Glutathione Transferase / metabolism
Green Fluorescent Proteins / metabolism
Image Processing, Computer-Assisted
Immunoprecipitation
Microscopy, Fluorescence
Microtubule-Associated Proteins / metabolism
Microtubules / metabolism
Models, Biological
Neoplasm Proteins
Plasmids / metabolism
Protein Binding
RNA, Small Interfering / metabolism
Recombinant Fusion Proteins / metabolism
Signal Transduction
Time Factors
Transfection
Vero Cells
Wound Healing
cdc42 GTP-Binding Protein / metabolism*
rac1 GTP-Binding Protein / metabolism*
ras GTPase-Activating Proteins / physiology*

Substances

Actins
Adenomatous Polyposis Coli Protein
IQ motif containing GTPase activating protein 1
Microtubule-Associated Proteins
Neoplasm Proteins
RNA, Small Interfering
Recombinant Fusion Proteins
ras GTPase-Activating Proteins
Green Fluorescent Proteins
cytoplasmic linker protein 170
Glutathione Transferase
cdc42 GTP-Binding Protein
rac1 GTP-Binding Protein