The assembly of tight junctions (TJs) and adherens junctions (AJs) is regulated by the transport of integral TJ and AJ proteins to and/or from the plasma membrane (PM) and it is tightly coordinated in epithelial cells. We previously reported that Rab13 and a junctional Rab13-binding protein (JRAB)/molecule interacting with CasL-like 2 (MICAL-L2) mediated the endocytic recycling of an integral TJ protein occludin and the formation of functional TJs. Here, we investigated the role of Rab13 and JRAB/MICAL-L2 in the transport of other integral TJ and AJ proteins claudin-1 and E-cadherin to the PM by using a Ca2+-switch model. Although knockdown of Rab13 specifically suppressed claudin-1 and occludin but not E-cadherin transport, knockdown of JRAB/MICAL-L2 and expression of its Rab13-binding domain (JRAB/MICAL-L2-C) inhibited claudin-1, occludin, and E-cadherin transport. We then identified Rab8 as another JRAB/MICAL-L2-C-binding protein. Knockdown of Rab8 inhibited the Rab13-independent transport of E-cadherin to the PM. Rab8 and Rab13 competed with each other for the binding to JRAB/MICAL-L2 and functionally associated with JRAB/MICAL-L2 at the perinuclear recycling/storage compartments and PM, respectively. These results suggest that the interaction of JRAB/MICAL-L2 with Rab8 and Rab13 coordinates the assembly of AJs and TJs.
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 MadinDarby canine kidney (MDCK) cells in response to 12-Otetradecanoylphorbol-13-acetate (TPA). Knockdown of Rab13 in canine MDCK cells suppressed the TPAinduced 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 cellcell 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.
Dear Editor, Papuloerythroderma of Ofuji (PEO) is characterized by the coalescence of solid papules leading to erythroderma, which spares the body folds, resulting in the so-called "deck-chair sign". PEO is of unknown etiology, but can be associated with medications and malignancies. Previous reports about druginduced PEO have suggested that T-helper (Th)2 cell polarization plays an important role in the pathogenesis of the condition. 1 PEO can also occur in cutaneous T-cell lymphoma, which is a Th2 cell malignancy. These findings prompted us to examine the importance of Th2 polarization in PEO. Therefore, we investigated the serum levels of thymus and activation regulated chemokine (TARC), a member of the Th2 chemokine family, in PEO patients. Serum TARC level can be high in inflammatory erythroderma 2 and drug-induced hypersensitivity syndrome which often progress to erythroderma. 3 Ten consecutive Japanese PEO patients (mean age, 80 years; range, 70-89; one woman and nine men) that were diagnosed and treated at our department from 2009 to 2012 were recruited. Patients with drug-induced or malignancyassociated PEO were excluded based on their medication profiles and computed tomography findings, respectively. The (a) (b) (c) Figure 1. (a) The patients' laboratory data. (b) Pretreatment clinical presentation of case 10. The patient's serum thymus and activation regulated chemokine (TARC) level was 20100 pg/mL at this point. (c) Clinical presentation of case 10 after 5 months' oral steroid treatment. The patient's skin eruptions had almost disappeared, and his serum TARC level had decreased to 1280 pg/mL. IgE, immunoglobulin E.
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