Gildor Boaz, Massarwa R'ada, Shilo Ben-Zion, Schejter Eyal D
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
EMBO Rep. 2009 Sep;10(9):1043-50. doi: 10.1038/embor.2009.129. Epub 2009 Jul 31.
The actin nucleation-promoting factors SCAR/WAVE and WASp, together with associated elements, mediate the formation of muscle fibres through myoblast fusion during Drosophila embryogenesis. Our phenotypic analysis, following the disruption of these two pathways, suggests that they function in a sequential manner. Suppressor of cyclic AMP receptor (SCAR) activity is required before the formation of pores in the membranes of fusing cells, whereas Wiskott-Aldrich syndrome protein (WASp) promotes the expansion of nascent pores and completion of the fusion process. Genetic epistasis experiments are consistent with this step-wise temporal progression. Our observations further imply a separate, Rac-dependent role for the SCAR complex in promoting myoblast migration. In keeping with the sequential utilization of the two systems, we observe abnormal accumulations of filamentous actin at the fusion sites when both pathways are disrupted, resembling those present when only SCAR-complex function is impaired. This observation further suggests that actin-filament accumulation at the fusion sites might not depend on Arp2/3 activity altogether.
肌动蛋白成核促进因子SCAR/WAVE和WASp以及相关元件，在果蝇胚胎发育过程中通过成肌细胞融合介导肌纤维的形成。我们对这两条途径进行破坏后的表型分析表明，它们以一种有序的方式发挥作用。在融合细胞的膜上形成孔之前，需要环磷酸腺苷受体抑制因子（SCAR）的活性，而威斯科特-奥尔德里奇综合征蛋白（WASp）则促进新生孔的扩张和融合过程的完成。基因上位性实验与这种逐步的时间进程一致。我们的观察结果进一步表明，SCAR复合物在促进成肌细胞迁移方面具有独立的、依赖Rac的作用。与这两个系统的顺序利用一致，当两条途径都被破坏时，我们在融合位点观察到丝状肌动蛋白的异常积累，类似于仅SCAR复合物功能受损时出现的情况。这一观察结果进一步表明，融合位点处肌动蛋白丝的积累可能并不完全依赖于Arp2/3活性。
