Involvement of heterophilic trans-interaction of Necl-5/Tage4/PVR/CD155 with nectin-3 in formation of nectin- and cadherin-based adherens junctions.
Nectins, Ca(2+)-independent immunoglobulin (Ig)-like cell-cell adhesion molecules and cadherins, Ca(2+)-dependent cell-cell adhesion molecules, are associated through their respective cytoplasmic tail-binding proteins, afadin and catenins and play roles in formation of adherens junctions (AJs) in epithelial cells and fibroblasts. Nectin-like molecule-5 (Necl-5) is a Ca(2+)-independent Ig-like molecule which does not homophilically trans-interact, but heterophilically trans-interacts with nectin-3, one member of the nectin family. Necl-5 does not directly bind afadin and therefore is not associated with cadherins. Necl-5 regulates cell motility and proliferation in cooperation with integrins and growth factor receptors, when it does not interact with nectin-3. We studied here a role of the heterophilic trans-interaction of Necl-5 with nectin-3 in cell-cell adhesion using L cells stably expressing Necl-5, nectin-3 and E-cadherin (Necl-5-nectin-3-EL cells). Afadin, E-cadherin and catenins were recruited to the nectin-3 side, but not to the Necl-5 side, of the contact sites formed by the heterophilic trans-interaction between Necl-5 and nectin-3. The anti-Necl-5 monoclonal antibody, which specifically inhibited the heterophilic trans-interaction of Necl-5 with nectin-3, inhibited the formation of the E-cadherin-based AJs in Necl-5-nectin-3-EL cells. These results indicate that Necl-5 plays roles not only in cell motility and proliferation but also in cell-cell adhesion in cooperation with nectin-3.
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan.
Tatsuhiro
T
Sato
Kenji
K
Irie
Takako
T
Ooshio
Wataru
W
Ikeda
Yoshimi
Y
Takai
D022005:Adherens Junctions / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D008840:Microfilament Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D000075983:Nectins; D011991:Receptors, Virus / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D051178:alpha Catenin; D051176:beta Catenin
D015820:Cadherins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D000075983:Nectins; D011991:Receptors, Virus; D015534:Trans-Activators; C108835:afadin; D051178:alpha Catenin; D051176:beta Catenin; C066100:poliovirus receptor