Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata, 700075, India.
Dev Dyn. 2023 Jul;252(7):986-1008. doi: 10.1002/dvdy.585. Epub 2023 Mar 23.
Drosophila Singed (mammalian Fascin) is an actin-binding protein that is known mainly for bundling parallel actin filaments. Among many functions of Singed, it is required for cell motility for both Drosophila and mammalian systems. Increased Fascin-1 levels positively correlate with greater metastasis and poor prognosis in human cancer. Border cell cluster, forms and migrates during Drosophila egg chamber development, shows higher expression of Singed compared with other follicle cells. Interestingly, loss of singed in border cells does not lead to any effect other than delay.
In this work, we have screened many actin-binding proteins in search of functional redundancy with Singed for border cell migration. We have found that Vinculin works with Singed to regulate border cell migration, albeit mildly. Although Vinculin is known for anchoring F-actin to the membrane, knockdown of both singed and vinculin leads to a reduced level of F-actin and changes in protrusion characteristics in border cells. We have also observed that they may act together to control microvilli length of brush border membrane vesicles and the shape of egg chambers in Drosophila.
We may conclude that singed and vinculin work together to control F-actin and these interactions are consistent across multiple platforms.
果蝇 Singed(哺乳动物 Fascin)是一种肌动蛋白结合蛋白,主要用于束绕平行的肌动蛋白丝。在 Singed 的众多功能中,它对于果蝇和哺乳动物系统的细胞运动都是必需的。Fascin-1 水平的增加与人类癌症的转移和预后不良呈正相关。在果蝇卵室发育过程中,边界细胞簇形成并迁移,其 Singed 的表达水平明显高于其他滤泡细胞。有趣的是,与其他滤泡细胞相比,边界细胞中 Singed 的缺失除了延迟外并没有导致任何其他影响。
在这项工作中,我们筛选了许多肌动蛋白结合蛋白,以寻找与 Singed 在边界细胞迁移中具有功能冗余性的蛋白。我们发现 Vinculin 与 Singed 一起调节边界细胞迁移,尽管作用较弱。尽管 Vinculin 以将 F-actin 锚定在膜上而闻名,但敲低 singed 和 vinculin 都会导致 F-actin 水平降低,并改变边界细胞的突起特征。我们还观察到,它们可能共同作用于控制果蝇中刷状缘膜泡的微绒毛长度和卵室的形状。
我们可以得出结论,singed 和 vinculin 共同作用来控制 F-actin,并且这些相互作用在多个平台上都是一致的。