Talamillo Ana, Sánchez Jonatan, Cantera Rafael, Pérez Coralia, Martín David, Caminero Eva, Barrio Rosa
Functional Genomics Unit, CIC bioGUNE, Technology Park, Building 801-A, 48160 DERIO, Bizkaia, Spain.
Development. 2008 May;135(9):1659-68. doi: 10.1242/dev.020685. Epub 2008 Mar 26.
Sumoylation, the covalent attachment of the small ubiquitin-related modifier SUMO to target proteins, regulates different cellular processes, although its role in the control of development remains unclear. We studied the role of sumoylation during Drosophila development by using RNAi to reduce smt3 mRNA levels in specific tissues. smt3 knockdown in the prothoracic gland, which controls key developmental processes through the synthesis and release of ecdysteroids, caused a 4-fold prolongation of larval life and completely blocked the transition from larval to pupal stages. The reduced ecdysteroid titer of smt3 knockdown compared with wild-type larvae explains this phenotype. In fact, after dietary administration of exogenous 20-hydroxyecdysone, knockdown larvae formed pupal cases. The phenotype is not due to massive cell death or degeneration of the prothoracic glands at the time when puparium formation should occur. Knockdown cells show alterations in expression levels and/or the subcellular localisation of enzymes and transcription factors involved in the regulation of ecdysteroid synthesis. In addition, they present reduced intracellular channels and a reduced content of lipid droplets and cholesterol, which could explain the deficit in steroidogenesis. In summary, our study indicates that Smt3 is required for the ecdysteroid synthesis pathway at the time of puparium formation.
SUMO化是指小泛素相关修饰物SUMO与靶蛋白的共价连接,它调控着不同的细胞过程,尽管其在发育控制中的作用仍不清楚。我们通过使用RNA干扰来降低特定组织中smt3 mRNA的水平,研究了SUMO化在果蝇发育过程中的作用。前胸腺通过合成和释放蜕皮激素来控制关键的发育过程,在前胸腺中敲低smt3会导致幼虫寿命延长4倍,并完全阻断幼虫向蛹期的转变。与野生型幼虫相比,敲低smt3后蜕皮激素滴度降低解释了这种表型。事实上,在通过饮食给予外源性20-羟基蜕皮激素后,敲低的幼虫形成了蛹壳。这种表型并不是由于在应该发生化蛹时前胸腺大量细胞死亡或退化所致。敲低的细胞显示出参与蜕皮激素合成调控的酶和转录因子的表达水平和/或亚细胞定位发生改变。此外,它们的细胞内通道减少,脂滴和胆固醇含量降低,这可以解释类固醇生成的缺陷。总之,我们的研究表明,在化蛹时,Smt3是蜕皮激素合成途径所必需的。