Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170.
Linkage of microtubules to special cortical regions is essential for cell polarization. CLIP-170 binds to the growing ends of microtubules and plays pivotal roles in orientation. We have found that IQGAP1, an effector of Rac1 and Cdc42, interacts with CLIP-170. In Vero fibroblasts, IQGAP1 localizes at the polarized leading edge. Expression of carboxy-terminal fragment of IQGAP1, which includes the CLIP-170 binding region, delocalizes GFP-CLIP-170 from the tips of microtubules and alters the microtubule array. Activated Rac1/Cdc42, IQGAP1, and CLIP-170 form a tripartite complex. Furthermore, expression of an IQGAP1 mutant defective in Rac1/Cdc42 binding induces multiple leading edges. These results indicate that Rac1/Cdc42 marks special cortical spots where the IQGAP1 and CLIP-170 complex is targeted, leading to a polarized microtubule array and cell polarization.
Department of Cell Pharmacology, Nagoya University, Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi 466-8550, Japan.
Masaki
M
Fukata
Takashi
T
Watanabe
Jun
J
Noritake
Masato
M
Nakagawa
Masaki
M
Yamaga
Shinya
S
Kuroda
Yoshiharu
Y
Matsuura
Akihiro
A
Iwamatsu
Franck
F
Perez
Kozo
K
Kaibuchi
D000199:Actins / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D016764:Cell Polarity; D048429:Cell Size; D002522:Chlorocebus aethiops; D046911:Macromolecular Substances; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism*; D009363:Neoplasm Proteins; D011485:Protein Binding; D011554:Pseudopodia / Q000737:chemistry / Q000378:metabolism; D014709:Vero Cells; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins
D000199:Actins; D002352:Carrier Proteins; C101203:IQ motif containing GTPase activating protein 1; D046911:Macromolecular Substances; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D020703:ras GTPase-Activating Proteins; C076744:cytoplasmic linker protein 170; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein