Critical role of the fifth domain of E-cadherin for heterophilic adhesion with αEβ7, but not for homophilic adhesion

Kiyono Shiraishi, Kensei Tsuzaka, Keiko Yoshimoto, Chika Kumazawa, Kyoko Nozaki, Tohru Abe, Kazuo Tsubota, Tsutomu Takeuchi

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The integrin αEβ7 is expressed on intestinal intraepithelial T lymphocytes and CD8+ T lymphocytes in inflammatory lesions near epithelial cells. Adhesion between αEβ7 + T and epithelial cells is mediated by the adhesive interaction of αEβ7 and E-cadherin; this interaction plays a key role in the damage of target epithelia. To explore the structure-function relationship of the heterophilic adhesive interaction between E-cadherin and αEβ 7, we performed cell aggregation assays using L cells transfected with an extracellular domain-deletion mutant of E-cadherin. In homophilic adhesion assays, L cells transfected with wild-type or a domain 5-deficient mutant formed aggregates, whereas transfectants with domain 1-, 2-, 3-, or 4-deficient mutants did not. These results indicate that not only domain 1, but domains 2, 3, and 4 are involved in homophilic adhesion. When αEβ7 + K562 cells were incubated with L cells expressing the wild type, 23% of the resulting cell aggregates consisted of αEβ7 + K562 cells. In contrast, the binding of αEβ7 + K562 cells to L cells expressing a domain 5-deficient mutant was significantly decreased, with αEβ7 + K562 cells accounting for only 4% of the cell aggregates, while homophilic adhesion was completely preserved. These results suggest that domain 5 is involved in heterophilic adhesion with αEβ7, but not in homophilic adhesion, leading to the hypothesis that the fifth domain of E-cadherin may play a critical role in the regulation of heterophilic adhesion to αEβ7 and may be a potential target for treatments altering the adhesion of αEβ7 + T cells to epithelial cells in inflammatory epithelial diseases.

Original languageEnglish
Pages (from-to)1014-1021
Number of pages8
JournalJournal of Immunology
Volume175
Issue number2
Publication statusPublished - 2005 Jul 15

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Cadherins
K562 Cells
T-Lymphocytes
Epithelial Cells
Adhesives
Cell Aggregation
Integrins
Epithelium

ASJC Scopus subject areas

  • Immunology

Cite this

Shiraishi, K., Tsuzaka, K., Yoshimoto, K., Kumazawa, C., Nozaki, K., Abe, T., ... Takeuchi, T. (2005). Critical role of the fifth domain of E-cadherin for heterophilic adhesion with αEβ7, but not for homophilic adhesion. Journal of Immunology, 175(2), 1014-1021.

Critical role of the fifth domain of E-cadherin for heterophilic adhesion with αEβ7, but not for homophilic adhesion. / Shiraishi, Kiyono; Tsuzaka, Kensei; Yoshimoto, Keiko; Kumazawa, Chika; Nozaki, Kyoko; Abe, Tohru; Tsubota, Kazuo; Takeuchi, Tsutomu.

In: Journal of Immunology, Vol. 175, No. 2, 15.07.2005, p. 1014-1021.

Research output: Contribution to journalArticle

Shiraishi, K, Tsuzaka, K, Yoshimoto, K, Kumazawa, C, Nozaki, K, Abe, T, Tsubota, K & Takeuchi, T 2005, 'Critical role of the fifth domain of E-cadherin for heterophilic adhesion with αEβ7, but not for homophilic adhesion', Journal of Immunology, vol. 175, no. 2, pp. 1014-1021.
Shiraishi K, Tsuzaka K, Yoshimoto K, Kumazawa C, Nozaki K, Abe T et al. Critical role of the fifth domain of E-cadherin for heterophilic adhesion with αEβ7, but not for homophilic adhesion. Journal of Immunology. 2005 Jul 15;175(2):1014-1021.
Shiraishi, Kiyono ; Tsuzaka, Kensei ; Yoshimoto, Keiko ; Kumazawa, Chika ; Nozaki, Kyoko ; Abe, Tohru ; Tsubota, Kazuo ; Takeuchi, Tsutomu. / Critical role of the fifth domain of E-cadherin for heterophilic adhesion with αEβ7, but not for homophilic adhesion. In: Journal of Immunology. 2005 ; Vol. 175, No. 2. pp. 1014-1021.
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