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Asef2 and Neurabin2 cooperatively regulate actin cytoskeletal organization and are involved in HGF-induced cell migration

Oncogene volume 28, pages 1357–1365 (2009)Cite this article

Abstract

The tumor suppressor adenomatous polyposis coli (APC) is mutated in sporadic and familial colorectal tumors. APC interacts with the Rac1- and Cdc42-specific guanine-nucleotide exchange factors (GEF), Asef and Asef2, which contain an APC-binding region (ABR) in addition to Dbl homology, Pleckstrin homology (PH) and Src homology 3 (SH3) domains. APC stimulates the GEF activity of Asef and Asef2, and thereby regulates cell adhesion and migration. Here we show that Asef2, but not Asef, interacts with Neurabin2/Spinophilin, a scaffold protein that binds to Filamentous actin (F-actin). In response to hepatocyte growth factor (HGF) treatment of HeLa cells, Asef2, Neurabin2 and APC were induced to accumulate and colocalize in lamellipodia and membrane ruffles. Neurabin2 did not affect the GEF activity of Asef2. RNA interference experiments showed that Asef2, Neurabin2 and APC are involved in HGF-induced cell migration. Furthermore, knockdown of Neurabin2 resulted in the suppression of Asef2-induced filopodia formation. These results suggest that Asef2, Neurabin2 and APC cooperatively regulate actin cytoskeletal organization and are required for HGF-induced cell migration.

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Acknowledgements

This work was supported by Grants-in-Aid for Scientific Research on Priority Areas and the Organization for Pharmaceutical Safety and Research, Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists, and in part by Global COE Program (Integrative Life Science Based on the Study of Biosignaling Mechanisms), MEXT, Japan.

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Authors and Affiliations

  1. Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan

    M Sagara, Y Kawasaki & T Akiyama

  2. Biomedicinal Information Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan

    S-i Iemura & T Natsume

  3. Division of Molecular and Cellular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan

    Y Takai

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  1. M Sagara
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  4. T Natsume
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Correspondence to T Akiyama.

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Sagara, M., Kawasaki, Y., Iemura, Si. et al. Asef2 and Neurabin2 cooperatively regulate actin cytoskeletal organization and are involved in HGF-induced cell migration. Oncogene 28, 1357–1365 (2009). https://doi.org/10.1038/onc.2008.478

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