A role for Drosophila IAP1-mediated caspase inhibition in Rac-dependent cell migration
A role for Drosophila IAP1-mediated caspase inhibition in Rac-dependent cell migration
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DOI：
10.1016/j.cell.2004.06.020
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发表时间：
2004-07-09
期刊：
影响因子：
64.5
通讯作者：
Montell, DJ
中科院分区：
文献类型：
--
作者：
Geisbrecht, ER;Montell, DJ
果蝇卵巢中的边缘细胞迁移是研究上皮细胞向迁移细胞转化的一个相对简单和遗传上容易处理的模型。像许多细胞迁移一样，边界细胞迁移受到显性-负性形式的GTP酶RAC的抑制。为了确定在RAC依赖的细胞运动中起作用的新基因，我们筛选了当过度表达时抑制显性负RAC引起的迁移缺陷的基因。由Thin(Th)基因编码的果蝇凋亡抑制因子1(DIAP1)的过表达抑制了迁移缺陷。此外，TH的功能缺失突变导致了迁移缺陷，但令人惊讶的是，它并没有导致细胞凋亡。影响上游caspase Dronc激活剂Dark蛋白的突变也挽救了racN17的迁移缺陷。这些结果表明DIAP1介导的Dronc抑制在Rac介导的细胞运动中具有不依赖于细胞凋亡的作用。
Border cell migration in the Drosophila ovary is a relatively simple and genetically tractable model for studying the conversion of epithelial cells to migratory cells. Like many cell migrations, border cell migration is inhibited by a dominant-negative form of the GTPase Rac. To identify new genes that function in Rac-dependent cell motility, we screened for genes that when overexpressed suppressed the migration defect caused by dominant-negative Rac. Overexpression of the Drosophila inhibitor of apoptosis 1 (DIAP1), which is encoded by the thread (th) gene, suppressed the migration defect. Moreover, loss-of-function mutations in th caused migration defects but, surprisingly, did not cause apoptosis. Mutations affecting the Dark protein, an activator of the upstream caspase Dronc, also rescued RacN17 migration defects. These results indicate an apoptosis-independent role for DIAP1-mediated Dronc inhibition in Rac-mediated cell motility.