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Antagonistic and agonistic effects of an extracellular fragment of nectin on formation of E‐cadherin‐based cell‐cell adhesion
Author(s) -
Honda Tomoyuki,
Shimizu Kazuya,
Kawakatsu Tomomi,
Yasumi Masato,
Shingai Tatsushi,
Fukuhara Atsunori,
OzakiKuroda Kumi,
Irie Kenji,
Nakanishi Hiroyuki,
Takai Yoshimi
Publication year - 2003
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1046/j.1365-2443.2003.00616.x
Subject(s) - nectin , cadherin , adherens junction , microbiology and biotechnology , biology , cell adhesion molecule , cell adhesion , cell–cell interaction , actin cytoskeleton , adhesion , cell , cytoskeleton , chemistry , biochemistry , organic chemistry
Background: Nectin is a Ca 2+ ‐independent immunoglobulin‐like cell‐cell adhesion molecule at the E‐cadherin‐based cell‐cell adherens junctions (AJs), and comprises a family consisting of four members, nectin‐1, ‐2, ‐3, and ‐4. Nectin and E‐cadherin are associated with afadin and α‐catenin, actin filament (F‐actin)‐binding proteins connecting respective adhesion molecules to the actin cytoskeleton, but the role of nectin in the formation of the E‐cadherin‐based cell‐cell AJs has not yet been fully understood. To obtain evidence for this role of nectin, we attempted to develop an antagonist and/or agonist of nectin. Results: We made a recombinant extracellular fragment of nectin‐3 (Nef‐3). Nef‐3 trans ‐interacted with cellular nectin‐1 and thereby diminished the formation of the nectin‐1‐based cell‐cell adhesion. This resulted in a reduction of the formation of the E‐cadherin‐based cell‐cell adhesion in L fibroblasts stably expressing both exogenous nectin‐1α and E‐cadherin (nectin‐1‐EL cells) and MDCK cells stably expressing exogenous nectin‐1α (nectin‐1‐MDCK cells). This antagonistic effect of Nef‐3 was also observed in L cells stably expressing exogenous E‐cadherin alone (EL cells) and wild‐type MDCK cells. Conversely, Nef‐3 coated on microbeads first recruited the nectin–afadin complex and then the E‐cadherin–catenin complex to the bead‐cell contact sites in nectin‐1‐EL and nectin‐1‐MDCK cells. Conclusion: These results suggest that nectin is necessary and sufficient for the recruitment of E‐cadherin to the nectin‐based cell‐cell adhesion sites and involved in the formation of E‐cadherin‐based cell‐cell AJs.