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

Research output: Contribution to journalArticle

354 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)871-883
Number of pages13
JournalDevelopmental Cell
Volume7
Issue number6
DOIs
Publication statusPublished - 12-2004

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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