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E-cadherin functions as a cis-dimer at the cell–cell adhesive interface in vivo

Nature Structural Biology volume 6, pages 310–312 (1999)Cite this article

Cadherins are homophilic calcium-dependent cell–cell adhesion molecules involved in specific cell recognition1,2. Recent studies of the three-dimensional structure of cadherin3,4 suggest that the cadherin extracellular domain forms a parallel dimer. However, to date no evidence has been reported for the existence of this parallel dimer in vivo and details of how this dimer formation is regulated are still fragmentary5,6. Here, using chemical crosslinking, we confirmed that E-cadherin forms a parallel (or 'cis') dimer (consisting of two molecules on the same cell surface) in the presence of calcium in vivo. We also investigated a possible relationship between cis-dimer formation and the cell adhesive state in vivo. Interestingly, in several human tumor cell lines that express E-cadherin normally but nevertheless exhibit a decreased adhesive function, we were unable to detect the cis-dimer by our crosslinking assay. Taken together, these data suggest that the cis-dimer of E-cadherin is a fundamental unit at the cell–cell adhesive interface in vivo.

Crosslinking cadherin in vivo

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Figure 1: Immunoblot (IB) analysis of dithio-bis-sulfosuccinimidyl propionate (DTSSP)- crosslinked products on the ELβ1 cell surface.
Figure 2: Correlations between the cell adhesion state and cis-dimer formation of E-cadherin in ELβ1 cells.

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Acknowledgements

We thank M. Mareel and M. Takeichi for providing the antibodies and cells, and H. Ohta, K. Osawa and K. Sakamoto for useful advice on the chemical crosslinking analysis.

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  1. Hiroshi Takeda

    Present address: National Food Research Institute, 2-1-2 Kannondai, Tsukuba, Ibaraki, 305, Japan

Authors and Affiliations

  1. Hirohashi Cell Configuration Project, Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology Corporation (JST), Tsukuba Research Consortium, 5-9-4 Tokodai, Tsukuba, 300-26, Japan

    Hiroshi Takeda, Yutaka Shimoyama & Setsuo Hirohashi

  2. Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, 606, Kyoto, Japan

    Akira Nagafuchi

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  1. Hiroshi Takeda
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  4. Setsuo Hirohashi
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Correspondence to Hiroshi Takeda.

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Takeda, H., Shimoyama, Y., Nagafuchi, A. et al. E-cadherin functions as a cis-dimer at the cell–cell adhesive interface in vivo. Nat Struct Mol Biol 6, 310–312 (1999). https://doi.org/10.1038/7542

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