Letter abstract
Nature Cell Biology 7, 270 - 277 (2005)
Published online: 20 February 2005 | doi:10.1038/ncb1227
PAR-6–PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiam1
Takashi Nishimura1, Tomoya Yamaguchi1, Katsuhiro Kato1, Masato Yoshizawa2, Yo-ichi Nabeshima2, Shigeo Ohno3, Mikio Hoshino2,4 & Kozo Kaibuchi1
A polarity complex of PAR-3, PAR-6 and atypical protein kinase C (aPKC) functions in various cell-polarization events, including neuron specification1, 2, 3, 4. The small GTPase Cdc42 binds to PAR-6 and regulates cell polarity. However, little is known about the downstream signals of the Cdc42–PAR protein complex. Here, we found that PAR-3 directly interacted with STEF/Tiam1, which are Rac-specific guanine nucleotide-exchange factors, and that STEF formed a complex with PAR-3–aPKC–PAR-6–Cdc42-GTP. Cdc42 induces lamellipodia in a Rac-dependent manner in N1E-115 neuroblastoma cells. Disruption of Cdc42–PAR-6 or PAR-3–STEF binding inhibited Cdc42-induced lamellipodia but not filopodia. The isolated STEF-binding PAR-3 fragment was sufficient to induce lamellipodia independently of Cdc42 and PAR-6. PAR-3 is required for Cdc42-induced Rac activation, but is not essential for lamellipodia formation itself. In cultured hippocampal neurons, STEF accumulated at the tip of the growing axon and colocalized with PAR-3. The spatio-temporal activation and signalling of Cdc42–PAR-6–PAR-3–STEF/Tiam1–Rac seem to be involved in neurite growth and axon specification. We propose that the PAR-6–PAR-3 complex mediates Cdc42-induced Rac activation by means of STEF/Tiam1, and that this process seems to be required for the establishment of neuronal polarity.
- Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa, Nagoya, Aichi 466-8550, Japan.
- Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
- Department of Molecular Biology, Yokohama City University School of Medicine, Fuku-ura 3-9, Kanazawa-ku, Yokohama 236-0004, Japan.
- PRESTO, JST, 4-1-8 Honcho Kawaguchi, Saitama, 332-0012 Japan.
Correspondence to: Kozo Kaibuchi1 e-mail: kaibuchi@med.nagoya-u.ac.jp
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Pars and polarity: taking control of RacNature Cell Biology News and Views (01 Mar 2005)
Neurobiology Getting axons goingNature News and Views (04 Aug 2005)
See all 3 matches for News And ViewsRESEARCH
Par-3 controls tight junction assembly through the Rac exchange factor Tiam1Nature Cell Biology Letter (01 Mar 2005)
The polarity protein PAR-3 and TIAM1 cooperate in dendritic spine morphogenesisNature Cell Biology Article (01 Mar 2006)
See all 30 matches for Research
