IQGAP3, a novel effector of Rac1 and Cdc42, regulates neurite outgrowth
IQGAP3, a novel effector of Rac1 and Cdc42, regulates neurite outgrowth
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DOI：
10.1242/jcs.03356
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发表时间：
2007-02-15
影响因子：
4
通讯作者：
Kaibuchi, Kozo
中科院分区：
文献类型：
--
作者：
Wang, Shujie;Watanabe, Takashi;Kaibuchi, Kozo
Rac1 和 Cdc42 是 Rho 家族 GTPases 的成员，通过其效应子控制多种细胞过程，例如细胞迁移和形态发生。在效应子中，IQGAP1 在各种细胞的细胞骨架结构和细胞间粘附的建立中发挥着关键作用。然而，其作用仍有待阐明，特别是在神经元细胞中。我们已确定 IQGAP3 是 IQGAP 家族的新成员，它在大脑中高表达。我们发现 IQGAP3 是 Rac1 和 Cdc42 的效应子，直接与肌动蛋白丝相关，并在海马神经元轴突的远端区域不对称地积累。 IQGAP3 的缺失会损害细胞骨架紊乱的神经元细胞中的神经突或轴突生长，但 IQGAP1 的缺失则不会。此外，IQGAP3 对于 Rac1/Cdc42 促进 PC12 细胞中的神经突生长是不可或缺的。综上所述，这些结果表明 IQGAP3 可以在神经元形态发生过程中将 Rac1 和 Cdc42 的激活与细胞骨架结构联系起来。
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.