Kunte Amit S, Matthews Krista A, Rawson Robert B
Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390, USA.
Cell Metab. 2006 Jun;3(6):439-48. doi: 10.1016/j.cmet.2006.04.011.
SREBPs are membrane bound transcription factors that are crucial for normal lipid synthesis in animal cells. Here, we show that Drosophila lacking dSREBP die before the third larval instar. Mutant larvae exhibit pronounced growth defects prior to lethality, along with substantial deficits in the transcription of genes required for fatty acid synthesis. Compared to wild-type larvae, mutants contain markedly less fatty acid, although its composition is unaltered. Dietary supplementation with fatty acids rescues mutants to adulthood. The most effective fatty acid, oleate, rescues 80% of homozygotes. Rescue by dSREBP requires expression only in fat body and gut. Larvae expressing dSREBP prior to pupariation complete development and are viable as adults even when dSREBP expression is subsequently extinguished. The role, if any, of dSREBP in adults is not yet apparent. These data indicate that dSREBP deficiency renders Drosophila larvae auxotrophic for fatty acids.
固醇调节元件结合蛋白（SREBPs）是膜结合转录因子，对动物细胞中的正常脂质合成至关重要。在此，我们表明缺乏dSREBP的果蝇在三龄幼虫之前死亡。突变幼虫在致死前表现出明显的生长缺陷，同时脂肪酸合成所需基因的转录也存在显著缺陷。与野生型幼虫相比，突变体含有的脂肪酸明显更少，但其组成未改变。通过饮食补充脂肪酸可使突变体存活至成年。最有效的脂肪酸油酸可挽救80%的纯合子。dSREBP的挽救作用仅需要在脂肪体和肠道中表达。在化蛹前表达dSREBP的幼虫能够完成发育，即使随后dSREBP表达消失，成虫也能存活。dSREBP在成虫中的作用（如果有的话）尚不明显。这些数据表明，dSREBP缺乏使果蝇幼虫对脂肪酸产生营养缺陷。
