Coendocytosis of cadherin and c-Met coupled to disruption of cell-cell adhesion in MDCK cells – regulation by Rho, Rac and Rab small G proteins (original) (raw)

• Original Paper
• Published: 19 November 1999
• Takashi Matozaki1,
• Toshiaki Sakisaka1,
• Atsuko Kodama1,
• Shigekazu Yokoyama1,
• Ying-Feng Peng1,
• Katsutoshi Nakano1,
• Kenji Takaishi1 &
• …
• Yoshimi Takai1

Oncogene volume 18, pages 6776–6784 (1999)Cite this article

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Abstract

Both E-cadherin, a cell-cell adhesion molecule, and c-Met, the hepatocyte growth factor (HGF)/scatter factor (SF) receptor, were colocalized at cell-cell adhesion sites of MDCK cells. HGF/SF or a phorbol ester, 12-**O**-tetradecanoylphorbol-13-acetate (TPA), induced disruption of cell-cell adhesion, which was accompanied by endocytosis of both E-cadherin and c-Met. Reduction of medium Ca2+ to a micromolar range showed the same effects. Re-increase in medium Ca2+ to a millimolar range formed cell-cell adhesion, which was accompanied by exocytosis of E-cadherin and c-Met, followed by their re-colocalization at the cell-cell adhesion sites. These results suggest that E-cadherin and c-Met are colocalized at cell-cell adhesion sites and undergo co-endo-exocytosis. We have previously shown that TPA does not induce disruption of cell-cell adhesion and subsequent scattering of MDCK cells stably expressing a dominant active mutant of RhoA or Rac1 small G protein or a dominant negative mutant of Rab5 small G protein. In these cell lines, the HGF- or TPA-induced coendocytosis of E-cadherin and c-Met was inhibited, but the coendocytosis of E-cadherin and c-Met in response to reduction of medium Ca2+ was not affected. Wortmannin, an inhibitor of phosphoinositide (PI) 3-kinase, inhibited the HGF-induced disruption of cell-cell junction and endocytosis of E-cadherin and c-Met, but not the TPA-induced ones. These results suggest that disruption of cell-cell adhesion is involved in the HGF- or TPA-induced coendocytosis of E-cadherin and c-Met in MDCK cells, and that the Rho and Rab family members indirectly regulate this coendocytosis. In addition, coendocytosis of E-cadherin and c-Met in response to HGF is partly mediated by PI 3-kinase. The cross-talk between cell-cell and cell-matrix adherens junctions is discussed.

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Acknowledgements

We thank Dr W Birchmeier (Max-Delbruck-Center for Molecular Medicine, Berlin, Germany) for providing MDCK cells, Dr S Nagata (Osaka University, Osaka, Japan) for the pEF-BOS expression plasmid, Dr M Zerial (European Molecular Biology Laboratory, Heidelberg, Germany) for the cDNA of N34Rab5, and Dr T Nakamura (Osaka University, Osaka, Japan) for HGF/SF. This investigation was supported by grants-in-aid for scientific research and for cancer research from the Ministry of Education, Science, Sports and Culture, Japan (1998, 1999) and by grants from the Human Frontier Science Program (1998).

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1. Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, 565-0871, Suita, Japan
   Takashi Kamei, Takashi Matozaki, Toshiaki Sakisaka, Atsuko Kodama, Shigekazu Yokoyama, Ying-Feng Peng, Katsutoshi Nakano, Kenji Takaishi & Yoshimi Takai

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1. Takashi Kamei
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2. Takashi Matozaki
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3. Toshiaki Sakisaka
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4. Atsuko Kodama
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5. Shigekazu Yokoyama
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6. Ying-Feng Peng
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7. Katsutoshi Nakano
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8. Kenji Takaishi
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9. Yoshimi Takai
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Kamei, T., Matozaki, T., Sakisaka, T. et al. Coendocytosis of cadherin and c-Met coupled to disruption of cell-cell adhesion in MDCK cells – regulation by Rho, Rac and Rab small G proteins.Oncogene 18, 6776–6784 (1999). https://doi.org/10.1038/sj.onc.1203114

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• Received: 04 June 1999
• Revised: 17 July 1999
• Accepted: 02 August 1999
• Published: 19 November 1999
• Issue Date: 18 November 1999
• DOI: https://doi.org/10.1038/sj.onc.1203114

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