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Involvement of Rab13 and JRAB/MICAL-L2 in epithelial cell scattering

Oncogene volume 27, pages 1687–1695 (2008)Cite this article

Abstract

Epithelial cell scattering recapitulates the first steps of carcinoma invasion/metastasis. While the balance between cell–cell adhesive activity and cell motility ultimately determines this process, its molecular mechanisms remain unclear. Adherence junctions and tight junctions (TJs) are primarily responsible for cell–cell adhesive activity and subjected to dynamic remodeling. We previously showed that Rab13 and its effector protein JRAB/MICAL-L2 mediate the endocytic recycling of the integral TJ protein occludin and the assembly of functional TJs. In this study, we examined the role of Rab13 and JRAB/MICAL-L2 in the scattering of Madin-Darby canine kidney (MDCK) cells in response to 12-O-tetradecanoylphorbol-13-acetate (TPA). Knockdown of Rab13 in canine MDCK cells suppressed the TPA-induced scattering, and this phenotype was restored by re-expression of human Rab13. During TPA-induced MDCK cell scattering, Rab13 was transiently activated and returned to its basal level, and both Rab13 and JRAB/MICAL-L2 were colocalized with F-actin at cell–cell contact sites and then accumulated at emerging lamellipodial structures. TPA-induced MDCK cell scattering was also inhibited by knockdown of canine JRAB/MICAL-L2 and rescued by re-expression of mouse JRAB/MICAL-L2. These results indicate that Rab13 and JRAB/MICAL-L2 are involved in epithelial cell scattering.

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Acknowledgements

We thank Dr W Birchmeier (Max Delbrueck Center for Molecular Medicine, Berlin, Germany) for the MDCK cells. This study was supported by Grants-in-Aid for Scientific Research (18590271 to NN and 15079207 and 18390089 to TS) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Department of Biochemistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan

    I Kanda, N Nishimura, H Nakatsuji, R Yamamura & T Sasaki

  2. Department of Plastic and Reconstructive Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan

    I Kanda & H Nakanishi

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  1. I Kanda
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Correspondence to T Sasaki.

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Kanda, I., Nishimura, N., Nakatsuji, H. et al. Involvement of Rab13 and JRAB/MICAL-L2 in epithelial cell scattering. Oncogene 27, 1687–1695 (2008). https://doi.org/10.1038/sj.onc.1210812

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