Translocation of the Dictyostelium TRAP1 homologue to mitochondria induces a novel prestarvation response
Translocation of the Dictyostelium TRAP1 homologue to mitochondria induces a novel prestarvation response
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DOI：
10.1242/jcs.01499
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发表时间：
2004-11-15
影响因子：
4
通讯作者：
Maeda, Y
中科院分区：
文献类型：
--
作者：
Morita, T;Amagai, A;Maeda, Y
Dd-TRAP 1是肿瘤坏死因子受体相关蛋白1（TRAP-1）的网骨藻同源物。Dd-TRAP 1位于低密度生长的细胞的皮层中，但发现在一种新的预饥饿因子的帮助下被易位到线粒体中，所述预饥饿因子随着细胞密度的增加而沿着在生长培养基中积累。Dd-TRAP 1敲低突变体（TRAP 1-RNAi细胞）在饥饿前反应中表现出明显缺陷。尽管TRAP 1-RNAi细胞显示出经典的预饥饿基因[dscA（discoidin I）和car 1（carA; cAMP受体）]的正常表达，但由预饥饿反应诱导的分化相关基因（dia 1和dia 3）的表达被显著抑制。相比之下，过表达Dd-TRAP 1的转化体表现出早期的预饥饿反应，并以细胞密度依赖的方式增加了dia 1和dia 3的表达。重要的是，将Dd-TRAP 1抗体导入D.结果表明，电穿孔法诱导的Dd-TRAP 1基因转染discoideum Ax-2细胞后，抑制了Dd-TRAP 1基因从皮层向线粒体的转移，从而大大抑制了分化的启动。综上所述，这些结果表明，Dd-TRAP 1是易位到线粒体的细胞密度在生长培养基中的传感器，并通过一种新的prestarvation响应增强早期发育程序。
Dd-TRAP1 is a Dictyostelium homologue of tumor necrosis factor receptor-associated protein 1 (TRAP-1). Dd-TRAP1 is located in the cortex of cells growing at a low density, but was found to be translocated to mitochondria with the help of a novel prestarvation factor that was accumulated in growth medium along with increased cell densities. The knockdown mutant of Dd-TRAP1 (TRAP1-RNAi cells) exhibited a significant defect in prestarvation response. Although TRAP1-RNAi cells showed normal expressions of classical prestarvation genes [dscA (discoidin I) and car1 (carA; cAMP receptor)], the expression of differentiation-associated genes (dia1 and dia3) induced by the prestarvation response were markedly repressed. By contrast, transformants overexpressing Dd-TRAP1 showed an early prestarvation response and also increased expression of dia1 and dia3 in a cell-density-dependent manner. Importantly, introduction of Dd-TRAP1 antibody into D. discoideum Ax-2 cells by electroporation inhibited the translocation of Dd-TRAP1 from the cortex to mitochondria and greatly inhibited the initiation of differentiation. Taken together, these results indicate that Dd-TRAP1 is translocated to mitochondria by sensing the cell density in growth medium and enhances the early developmental program through a novel prestarvation response.