Department of Bioscience, Kwansei Gakuin University, 2-1 Gakuen, Sanda 669-1337, Japan.
Development. 2011 Sep;138(18):4013-23. doi: 10.1242/dev.059568. Epub 2011 Aug 10.
Cytoskeletal regulation is important in cell migration. The Caenorhabditis elegans gonadal distal tip cells (DTCs) offer a simple model with which to investigate the mechanism of cell migration in organogenesis. Here, we report that one of the spectraplakin isoforms, VAB-10B1, plays an essential role in cell and nuclear migration of DTCs by regulating the actin and microtubule (MT) cytoskeleton. In the vab-10(tk27) mutant, which lacks VAB-10B1, alignment of filamentous (F)-actin and MTs was weakly and severely disorganized, respectively, which resulted in a failure to translocate the DTC nucleus and a premature termination of DTC migration. An MT growing-tip marker, EBP-2-GFP, revealed that polarized outgrowth of MTs towards the nuclei of migrating DTCs was strikingly impaired in tk27 animals. A vab-10 mini-gene encoding only the actin- and MT-binding domains significantly rescued the gonadal defects, suggesting that VAB-10B1 has a role in linking actin and MT filaments. These results suggest that VAB-10B1/spectraplakin regulates the polarized alignment of MTs, possibly by linking F-actin and MTs, which enables normal nuclear translocation and cell migration of DTCs.
细胞骨架的调节在细胞迁移中很重要。秀丽隐杆线虫的性腺远端 tip 细胞 (DTC) 提供了一个简单的模型,可用于研究器官发生中细胞迁移的机制。在这里,我们报告说,spectraplakin 同工型之一 VAB-10B1 通过调节肌动蛋白和微管 (MT) 细胞骨架在 DTCs 的细胞和核迁移中发挥重要作用。在缺乏 VAB-10B1 的 vab-10(tk27) 突变体中,丝状 (F)-肌动蛋白和 MT 的排列分别严重和轻度紊乱,导致 DTC 核无法迁移和 DTC 迁移过早终止。一个 MT 生长尖端标记物 EBP-2-GFP 表明,在 tk27 动物中,向迁移的 DTC 细胞核极化的 MT 生长明显受损。仅编码肌动蛋白和 MT 结合结构域的 vab-10 微基因显著挽救了性腺缺陷,表明 VAB-10B1 在连接肌动蛋白和 MT 丝方面发挥作用。这些结果表明,VAB-10B1/spectraplakin 调节 MT 的极化排列,可能通过连接 F-肌动蛋白和 MT,从而使 DTC 的正常核易位和细胞迁移成为可能。