Regulation of E-cadherin endocytosis by nectin through afadin, Rap1, and p120ctn.
Adherens junctions (AJs) are a major cell-cell adhesion structure in epithelial cells that are formed by two major cell-cell adhesion molecules, E-cadherin and nectin. We have previously shown that nectin first forms cell-cell adhesion and then recruits non-trans-interacting E-cadherin to the nectin-based cell-cell adhesion sites, which gradually trans-interact there, eventually forming AJs. We have examined here the effect of trans-interacting nectin on non-trans-interacting E-cadherin endocytosis. Trans-interacting nectin capable of associating with afadin, but not trans-interacting nectin mutant incapable of associating with afadin, inhibited non-trans-interacting E-cadherin endocytosis in intact cells. Afadin is a nectin- and actin filament-binding protein that connects nectin to the actin cytoskeleton. Studies on the mode of action of the nectin-afadin system using cell-free assay revealed that afadin associated with nectin bound Rap1 activated by trans-interacting nectin, interacted with p120ctn, and strengthened the binding of p120ctn to E-cadherin, eventually reducing non-trans-interacting E-cadherin endocytosis. Afadin, which did not bind Rap1, was inactive in this capacity. These results indicate that trans-interacting nectin inhibits non-trans-interacting E-cadherin endocytosis through afadin, Rap1, and p120ctn and thereby further accumulates non-trans-interacting E-cadherin to the nectin-based cell-cell adhesion sites for the formation of AJs.
Hoshino
Takashi
T
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Osaka 565-0871, Japan.
Sakisaka
Toshiaki
T
Baba
Takeshi
T
Yamada
Tomohiro
T
Kimura
Toshihiro
T
Takai
Yoshimi
Y
D015820:Cadherins / Q000502:physiology*; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002460:Cell Line; D004705:Endocytosis / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D016547:Kinesins; D008840:Microfilament Proteins / Q000502:physiology*; D008856:Microscopy, Fluorescence; D009218:Myosins; D000075983:Nectins; D010750:Phosphoproteins / Q000502:physiology*; D011485:Protein Binding; D020827:rap1 GTP-Binding Proteins / Q000502:physiology*; D000095002:Delta Catenin
C095516:AFDN protein, human; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D000075983:Nectins; D010750:Phosphoproteins; C108835:afadin; D009218:Myosins; D016547:Kinesins; D020827:rap1 GTP-Binding Proteins; D000095002:Delta Catenin; C000722347:CTNND1 protein, human