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Localization of p0071-interacting proteins, plakophilin-related armadillo-repeat protein-interacting protein (PAPIN) and ERBIN, in epithelial cells

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Abstract

PAPIN has six PDZ domains and interacts with p0071, a catenin-related protein. Recent studies have revealed that catenins determine the subcellular localization of some PDZ proteins. We have examined whether the localization of PAPIN is determined by p0071 in epithelial cells. PAPIN was localized not only on the lateral membrane but also on the apical membrane, where p0071 was absent. The targeting to both membranes was mediated by the middle region of PAPIN and did not require the p0071-interacting PDZ domain. In cells that came into contact, PAPIN was diffusely distributed on the plasma membrane, while p0071 was concentrated at immature cell–cell contacts. When epithelial cells were exposed to the low concentration of calcium, p0071 was internalized, whereas PAPIN remained on the plasma membrane. We also confirmed that the interaction with p0071 was not essential for the membrane targeting of ERBIN, a recently identified p0071- and ErbB2-binding protein. PAPIN, p0071, and ERBIN formed a complex in 293T cells. Furthermore, ERBIN and ErbB2 were colocalized with PAPIN on the lateral membrane. These findings suggest that PAPIN, p0071, and ERBIN come to the cell–cell contacts independently and interact with each other on the lateral membrane.

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Acknowledgements

This study was supported by grants-in-aids for Scientific Research and Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science, and Technology, a grant from NOVARTIS Foundation (Japan) for the Promotion of Science (1999), and a grant from Yamanouchi Foundation for Research on Metabolic Disorders (2000). We thank Dr Gary Nolan (Stanford University) for phoenix ampho cells. We also thank Ms C Rokukawa and Ms M Miyahara-Tenkatsu for skilful technical assistance.

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Authors and Affiliations

  1. Department of Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

    Hideki Ohno, Susumu Hirabayashi, Toshihiko Iizuka & Yutaka Hata

  2. Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

    Hideki Ohno & Hirohide Ohnishi

  3. Department of Nephrology and Endocrinology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

    Toshiro Fujita

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  1. Hideki Ohno
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  2. Susumu Hirabayashi
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  3. Toshihiko Iizuka
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  4. Hirohide Ohnishi
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  5. Toshiro Fujita
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  6. Yutaka Hata
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Correspondence to Yutaka Hata.

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Ohno, H., Hirabayashi, S., Iizuka, T. et al. Localization of p0071-interacting proteins, plakophilin-related armadillo-repeat protein-interacting protein (PAPIN) and ERBIN, in epithelial cells. Oncogene 21, 7042–7049 (2002). https://doi.org/10.1038/sj.onc.1205852

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