Regulation of epithelial wound closure and intercellular adhesion by interaction of AF6 with actin cytoskeleton.
AF6 is a human multi-domain protein involved in signaling and organization of cell junctions during embryogenesis. Its homologue in rat is called afadin. Three different AF6 transcripts are known, but only isoform 1 (AF6i1) has been characterized as protein. We focused on the AF6 isoform 3 (AF6i3), which differs from the AF6i1 by an additional C-terminal F-actin-binding site. Knockdown of AF6i3 in epithelial cells, which express only this isoform, resulted in impaired E-cadherin-dependent intercellular adhesion due to concomitantly reduced association of E-cadherin with F-actin and p120-catenin. Impaired intercellular adhesion also accelerated wound closure due to increased directionality of cell migration and delayed de novo formation of cell junctions. In contrast to AF6i3, the AF6i1 displayed a reduced association with the actin cytoskeleton and did not stabilize intercellular adhesion. Therefore, we propose that the AF6i3 protein stabilizes E-cadherin-dependent adhesion during dynamic processes, such as wound closure and formation of cell junctions, by linking the E-cadherin-catenin complex to the actin cytoskeleton via its F-actin-binding site.
Lorger
Mihaela
M
Institute of Medical Virology, University of Zurich, Gloriastrasse 30, CH-8006 Zurich, Switzerland.
Moelling
Karin
K
D000199:Actins / Q000378:metabolism*; D001665:Binding Sites; D001940:Breast / Q000166:cytology / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D051177:Catenins; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication; D002465:Cell Movement; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D007365:Intercellular Junctions; D007668:Kidney / Q000378:metabolism; D016547:Kinesins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009218:Myosins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D014945:Wound Healing; D000095002:Delta Catenin
C095516:AFDN protein, human; D000199:Actins; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; D009218:Myosins; D016547:Kinesins; D002118:Calcium; D000095002:Delta Catenin; C000722347:CTNND1 protein, human