Laboratory for Cell Fate Decision, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
Cell. 2011 Sep 16;146(6):942-54. doi: 10.1016/j.cell.2011.07.043.
Extrinsic signals received by a cell can induce remodeling of the cytoskeleton, but the downstream effects of cytoskeletal changes on gene expression have not been well studied. Here, we show that during telophase of an asymmetric division in C. elegans, extrinsic Wnt signaling modulates spindle structures through APR-1/APC, which in turn promotes asymmetrical nuclear localization of WRM-1/β-catenin and POP-1/TCF. APR-1 that localized asymmetrically along the cortex established asymmetric distribution of astral microtubules, with more microtubules found on the anterior side. Perturbation of the Wnt signaling pathway altered this microtubule asymmetry and led to changes in nuclear WRM-1 asymmetry, gene expression, and cell-fate determination. Direct manipulation of spindle asymmetry by laser irradiation altered the asymmetric distribution of nuclear WRM-1. Moreover, laser manipulation of the spindles rescued defects in nuclear POP-1 asymmetry in wnt mutants. Our results reveal a mechanism in which the nuclear localization of proteins is regulated through the modulation of microtubules.
细胞接收到的外在信号可以诱导细胞骨架的重塑，但细胞骨架变化对基因表达的下游影响尚未得到很好的研究。在这里，我们发现在秀丽隐杆线虫的不对称分裂的末期，外在的 Wnt 信号通过 APR-1/APC 来调节纺锤体结构，进而促进 WRH-1/β-连环蛋白和 POP-1/TCF 的不对称核定位。沿皮层不对称定位的 APR-1 建立了星状微管的不对称分布，在前侧发现了更多的微管。Wnt 信号通路的干扰改变了这种微管不对称性，并导致核 WRH-1 不对称性、基因表达和细胞命运决定的变化。通过激光照射直接操纵纺锤体的不对称性改变了核 WRH-1 的不对称分布。此外，激光操纵纺锤体挽救了 wnt 突变体中核 POP-1 不对称性的缺陷。我们的结果揭示了一种通过调节微管来调节蛋白质核定位的机制。
