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Centrosomal localization of Diversin and its relevance to Wnt signaling.

ABSTRACT: Wnt pathways regulate many developmental processes, including cell-fate specification, cell polarity, and cell movements during morphogenesis. The subcellular distribution of pathway mediators in specific cellular compartments might be crucial for the selection of pathway targets and signaling specificity. We find that the ankyrin-repeat protein Diversin, which functions in different Wnt signaling branches, localizes to the centrosome in Xenopus ectoderm and mammalian cells. Upon stimulation with Wnt ligands, the centrosomal distribution of Diversin is transformed into punctate cortical localization. Also, Diversin was recruited by Frizzled receptors to non-homogeneous Dishevelled-containing cortical patches. Importantly, Diversin deletion constructs, which did not localize to the centrosome, failed to efficiently antagonize Wnt signaling. Furthermore, a C-terminal construct that interfered with Diversin localization inhibited Diversin-mediated beta-catenin degradation. These observations suggest that the centrosomal localization of Diversin is crucial for its function in Wnt signaling.

SUBMITTER: Itoh K

PROVIDER: S-EPMC2758808 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Centrosomal localization of Diversin and its relevance to Wnt signaling.

Itoh Keiji K Jenny Andreas A Mlodzik Marek M Sokol Sergei Y SY

Journal of cell science 20090929 Pt 20

Wnt pathways regulate many developmental processes, including cell-fate specification, cell polarity, and cell movements during morphogenesis. The subcellular distribution of pathway mediators in specific cellular compartments might be crucial for the selection of pathway targets and signaling specificity. We find that the ankyrin-repeat protein Diversin, which functions in different Wnt signaling branches, localizes to the centrosome in Xenopus ectoderm and mammalian cells. Upon stimulation wit ...[more]

PMID: 19789178

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Project description:Macrophages, which exhibit great plasticity, are important components of the inflamed tissue and constitute an essential element of regenerative responses. Epithelial Wnt signalling is involved in mechanisms of proliferation and differentiation and expression of Wnt ligands by macrophages has been reported. We aim to determine whether the macrophage phenotype determines the expression of Wnt ligands, the influence of the macrophage phenotype in epithelial activation of Wnt signalling and the relevance of this pathway in ulcerative colitis. Human monocyte-derived macrophages and U937-derived macrophages were polarized towards M1 or M2 phenotypes and the expression of Wnt1 and Wnt3a was analyzed by qPCR. The effects of macrophages and the role of Wnt1 were analyzed on the expression of ?-catenin, Tcf-4, c-Myc and markers of cell differentiation in a co-culture system with Caco-2 cells. Immunohistochemical staining of CD68, CD206, CD86, Wnt1, ?-catenin and c-Myc were evaluated in the damaged and non-damaged mucosa of patients with UC. We also determined the mRNA expression of Lgr5 and c-Myc by qPCR and protein levels of ?-catenin by western blot. Results show that M2, and no M1, activated the Wnt signaling pathway in co-culture epithelial cells through Wnt1 which impaired enterocyte differentiation. A significant increase in the number of CD206+ macrophages was observed in the damaged mucosa of chronic vs newly diagnosed patients. CD206 immunostaining co-localized with Wnt1 in the mucosa and these cells were associated with activation of canonical Wnt signalling pathway in epithelial cells and diminution of alkaline phosphatase activity. Our results show that M2 macrophages, and not M1, activate Wnt signalling pathways and decrease enterocyte differentiation in co-cultured epithelial cells. In the mucosa of UC patients, M2 macrophages increase with chronicity and are associated with activation of epithelial Wnt signalling and diminution in enterocyte differentiation.

Dataset Information

Centrosomal localization of Diversin and its relevance to Wnt signaling.

Publications

Centrosomal localization of Diversin and its relevance to Wnt signaling.

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