Involvement of Rab13 and JRAB/MICAL-L2 in epithelial cell scattering.
Epithelial cell scattering recapitulates the first steps of carcinoma invasion/metastasis. While the balance between cell-cell adhesive activity and cell motility ultimately determines this process, its molecular mechanisms remain unclear. Adherence junctions and tight junctions (TJs) are primarily responsible for cell-cell adhesive activity and subjected to dynamic remodeling. We previously showed that Rab13 and its effector protein JRAB/MICAL-L2 mediate the endocytic recycling of the integral TJ protein occludin and the assembly of functional TJs. In this study, we examined the role of Rab13 and JRAB/MICAL-L2 in the scattering of Madin-Darby canine kidney (MDCK) cells in response to 12-O-tetradecanoylphorbol-13-acetate (TPA). Knockdown of Rab13 in canine MDCK cells suppressed the TPA-induced scattering, and this phenotype was restored by re-expression of human Rab13. During TPA-induced MDCK cell scattering, Rab13 was transiently activated and returned to its basal level, and both Rab13 and JRAB/MICAL-L2 were colocalized with F-actin at cell-cell contact sites and then accumulated at emerging lamellipodial structures. TPA-induced MDCK cell scattering was also inhibited by knockdown of canine JRAB/MICAL-L2 and rescued by re-expression of mouse JRAB/MICAL-L2. These results indicate that Rab13 and JRAB/MICAL-L2 are involved in epithelial cell scattering.
Kanda
I
I
Department of Biochemistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Nishimura
N
N
Nakatsuji
H
H
Yamamura
R
R
Nakanishi
H
H
Sasaki
T
T
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000502:physiology*; D004285:Dogs; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008840:Microfilament Proteins / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D020691:rab GTP-Binding Proteins / Q000502:physiology*
D002273:Carcinogens; D003598:Cytoskeletal Proteins; C512298:JRAB protein, mouse; C528177:MICALL2 protein, human; D008840:Microfilament Proteins; C085485:RAB13 protein, human; D020691:rab GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate