Patel Falshruti B, Bernadskaya Yelena Y, Chen Esteban, Jobanputra Aesha, Pooladi Zahra, Freeman Kristy L, Gally Christelle, Mohler William A, Soto Martha C
Department of Pathology and Laboratory Medicine, UMDNJ - Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA.
Dev Biol. 2008 Dec 15;324(2):297-309. doi: 10.1016/j.ydbio.2008.09.023. Epub 2008 Oct 2.
The WAVE/SCAR complex promotes actin nucleation through the Arp2/3 complex, in response to Rac signaling. We show that loss of WVE-1/GEX-1, the only C. elegans WAVE/SCAR homolog, by genetic mutation or by RNAi, has the same phenotype as loss of GEX-2/Sra1/p140/PIR121, GEX-3/NAP1/HEM2/KETTE, or ABI-1/ABI, the three other components of the C. elegans WAVE/SCAR complex. We find that the entire WAVE/SCAR complex promotes actin-dependent events at different times and in different tissues during development. During C. elegans embryogenesis loss of CED-10/Rac1, WAVE/SCAR complex components, or Arp2/3 blocks epidermal cell migrations despite correct epidermal cell differentiation. 4D movies show that this failure occurs due to decreased membrane dynamics in specific epidermal cells. Unlike myoblasts in Drosophila, epidermal cell fusions in C. elegans can occur in the absence of WAVE/SCAR or Arp2/3. Instead we find that subcellular enrichment of F-actin in epithelial tissues requires the Rac-WAVE/SCAR-Arp2/3 pathway. Intriguingly, we find that at the same stage of development both F-actin and WAVE/SCAR proteins are enriched apically in one epithelial tissue and basolaterally in another. We propose that temporally and spatially regulated actin nucleation by the Rac-WAVE/SCAR-Arp2/3 pathway is required for epithelial cell organization and movements during morphogenesis.
WAVE/SCAR复合体通过Arp2/3复合体促进肌动蛋白成核，以响应Rac信号。我们发现，通过基因突变或RNA干扰使秀丽隐杆线虫唯一的WAVE/SCAR同源物WVE-1/GEX-1缺失，其表型与秀丽隐杆线虫WAVE/SCAR复合体的其他三个组分GEX-2/Sra1/p140/PIR121、GEX-3/NAP1/HEM2/KETTE或ABI-1/ABI缺失相同。我们发现，整个WAVE/SCAR复合体在发育过程中的不同时间和不同组织中促进肌动蛋白依赖性事件。在秀丽隐杆线虫胚胎发生过程中，尽管表皮细胞分化正常，但CED-10/Rac1、WAVE/SCAR复合体组分或Arp2/3的缺失会阻止表皮细胞迁移。四维电影显示，这种失败是由于特定表皮细胞中膜动力学降低所致。与果蝇中的成肌细胞不同，秀丽隐杆线虫的表皮细胞融合可以在没有WAVE/SCAR或Arp2/3的情况下发生。相反，我们发现上皮组织中F-肌动蛋白的亚细胞富集需要Rac-WAVE/SCAR-Arp2/3途径。有趣的是，我们发现在发育的同一阶段，F-肌动蛋白和WAVE/SCAR蛋白在上皮组织的一个部位顶端富集，而在另一个部位基底外侧富集。我们提出，Rac-WAVE/SCAR-Arp2/3途径在时间和空间上受调控的肌动蛋白成核对于形态发生过程中上皮细胞的组织和运动是必需的。
