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First published online 23 January 2007
doi: 10.1242/jcs.03356

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IQGAP3, a novel effector of Rac1 and Cdc42, regulates neurite outgrowth

Shujie Wang¹, Takashi Watanabe¹, Jun Noritake¹, Masaki Fukata^1,*, Takeshi Yoshimura¹, Norimichi Itoh¹, Takumi Harada¹, Masato Nakagawa^1,, Yoshiharu Matsuura², Nariko Arimura¹ and Kozo Kaibuchi^1,

¹ Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan
² Research Center for Emerging Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Japan

Author for correspondence (e-mail: kaibuchi{at}med.nagoya-u.ac.jp)

Accepted 21 November 2006

Rac1 and Cdc42, members of the Rho family GTPases, control diverse cellular processes such as cell migration and morphogenesis through their effectors. Among the effectors, IQGAP1 plays pivotal roles in the establishment of cytoskeletal architecture and intercellular adhesions in various cells. However, its roles remain to be clarified, especially in neuronal cells. We have identified IQGAP3 as a novel member of the IQGAP family, which is highly expressed in brain. We found that IQGAP3, an effector of Rac1 and Cdc42, associates directly with actin filaments and accumulates asymmetrically at the distal region of axons in hippocampal neurons. The depletion of IQGAP3 impairs neurite or axon outgrowth in neuronal cells with the disorganized cytoskeleton, but depletion of IQGAP1 does not. Furthermore, IQGAP3 is indispensable for Rac1/Cdc42-promoted neurite outgrowth in PC12 cells. Taken together, these results indicate that IQGAP3 can link the activation of Rac1 and Cdc42 with the cytoskeletal architectures during neuronal morphogenesis.

Key words: IQGAP, Rho family GTPases, Cytoskeleton, Axon outgrowth

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