Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.
J Cell Sci. 2009 Oct 15;122(Pt 20):3791-8. doi: 10.1242/jcs.057067. Epub 2009 Sep 29.
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.
Wnt 通路调节许多发育过程，包括细胞命运特化、细胞极性和形态发生过程中的细胞运动。通路介质在特定细胞区室中的亚细胞分布对于选择通路靶标和信号特异性可能至关重要。我们发现，在不同的 Wnt 信号分支中起作用的锚蛋白重复蛋白 Diversin 定位于 Xenopus 外胚层和哺乳动物细胞的中心体。在受到 Wnt 配体刺激后，Diversin 的中心体分布被转化为点状皮质定位。此外，Diversin 被 Frizzled 受体募集到非均匀的含有 Dishevelled 的皮质斑块上。重要的是，不能定位于中心体的 Diversin 缺失构建体未能有效拮抗 Wnt 信号。此外，干扰 Diversin 定位的 C 末端构建体抑制了 Diversin 介导的β-连环蛋白降解。这些观察结果表明，Diversin 的中心体定位对于其在 Wnt 信号中的功能至关重要。
