Tage4/Nectin-like molecule-5 heterophilically trans-interacts with cell adhesion molecule Nectin-3 and enhances cell migration.
Malignant transformation of cells causes disruption of cell-cell adhesion, enhancement of cell motility, and invasion into surrounding tissues. Nectins have both homophilic and heterophilic cell-cell adhesion activities and organize adherens junctions in cooperation with cadherins. We examined here whether Tage4, which was originally identified to be a gene overexpressed in colon carcinoma and has a domain structure similar to those of nectins, is involved in cell adhesion and/or migration. Tage4 heterophilically trans-interacted with nectin-3, but not homophilically with Tage4. Expression of Tage4 was markedly elevated in NIH3T3 cells transformed by an oncogenic Ki-Ras (V12Ras-NIH3T3 cells) as compared with that of wild-type NIH3T3 cells. trans-Interaction of Tage4 with nectin-3 enhanced motility of V12Ras-NIH3T3 cells. Tage4 did not bind afadin, a nectin- and actin filament-binding protein that connects nectins to the actin cytoskeleton and cadherins through catenins. Thus, Tage4 heterophilically trans-interacts with nectin-3 and regulates cell migration. Tage4 is tentatively re-named here nectin-like molecule-5 (necl-5) on the basis of its function and domain structure similar to those of nectins.
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan.
Wataru
W
Ikeda
Shigeki
S
Kakunaga
Shinsuke
S
Itoh
Tatsushi
T
Shingai
Kyoji
K
Takekuni
Keiko
K
Satoh
Yoko
Y
Inoue
Akiko
A
Hamaguchi
Koji
K
Morimoto
Masakazu
M
Takeuchi
Toshio
T
Imai
Yoshimi
Y
Takai
D016475:3T3 Cells; D000818:Animals; D000951:Antigens, Neoplasm; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement; D003001:Cloning, Molecular; D003599:Cytoskeleton / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D016547:Kinesins; D007700:Kinetics; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism; D009218:Myosins; D000075983:Nectins; D009363:Neoplasm Proteins; D010802:Phylogeny; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D020349:Surface Plasmon Resonance; D013997:Time Factors; D014162:Transfection
C095516:AFDN protein, human; C490657:Afdn protein, mouse; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D008840:Microfilament Proteins; C000619014:NECTIN3 protein, human; C000619017:Nectin3 protein, mouse; D000075983:Nectins; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; C476587:Taa1 protein, mouse; C108835:afadin; D009218:Myosins; D016547:Kinesins