Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore.
Institut Curie, PSL Research University, Sorbonne Université, CNRS UMR144 "Cell Biology and Cancer", Paris, France.
PLoS One. 2019 Feb 22;14(2):e0212711. doi: 10.1371/journal.pone.0212711. eCollection 2019.
Wnts are a family of secreted palmitoleated glycoproteins that play key roles in cell to cell communication during development and regulate stem cell compartments in adults. Wnt receptors, downstream signaling cascades and target pathways have been extensively studied while less is known about how Wnts are secreted and move from producing cells to receiving cells. We used the synchronization system called Retention Using Selective Hook (RUSH) to study Wnt trafficking from endoplasmic reticulum to Golgi and then to plasma membrane and filopodia in real time. Inhibition of porcupine (PORCN) or knockout of Wntless (WLS) blocked Wnt exit from the ER. Wnt-containing vesicles paused at sub-cortical regions of the plasma membrane before exiting the cell. Wnt-containing vesicles were associated with filopodia extending to adjacent cells. These data visualize and confirm the role of WLS and PORCN in ER exit of Wnts and support the role of filopodia in Wnt signaling.
Wnts 是一类分泌型棕榈酰化糖蛋白家族，在发育过程中的细胞间通讯中发挥关键作用，并调节成体中的干细胞区室。Wnt 受体、下游信号级联和靶途径已得到广泛研究，而关于 Wnts 如何分泌并从产生细胞转移到接收细胞的研究较少。我们使用称为保留使用选择性钩 (RUSH) 的同步系统实时研究 Wnt 从内质网到高尔基体再到质膜和丝状伪足的运输。抑制刺猬 (PORCN) 或敲除 Wntless (WLS) 会阻止 Wnt 从内质网中逸出。含有 Wnt 的囊泡在离开细胞之前在质膜的皮质下区域暂停。含有 Wnt 的囊泡与延伸到相邻细胞的丝状伪足相关。这些数据可视化并证实了 WLS 和 PORCN 在 Wnt 从内质网逸出中的作用，并支持丝状伪足在 Wnt 信号中的作用。
