Tran Nancy L, Goldsmith Samuel L, Dimitriadou Agapi, Takaesu Norma T, Consoulas Christos, Newfeld Stuart J
School of Life Sciences, Arizona State University, Tempe AZ 85287-4501.
Medical School, National and Kapodistrian University of Athens, Athens, Greece.
G3 (Bethesda). 2018 Aug 30;8(9):2979-2990. doi: 10.1534/g3.118.200572.
CORL proteins (known as SKOR in mice, Fussel in humans and fussel in Flybase) are a family of CNS specific proteins related to Sno/Ski oncogenes. Their developmental and adult roles are largely unknown. A Drosophila (dCORL) reporter gene is expressed in all Drosophila insulin-like peptide 2 (dILP2) neurons of the pars intercerebralis (PI) of the larval and adult brain. The transcription factor Drifter is also expressed in the PI in a subset of dCORL and dILP2 expressing neurons and in several non-dILP2 neurons. mutant virgin adult brains are missing all dILP2 neurons that do not also express Drifter. This phenotype is also seen when expressing dCORL-RNAi in neurosecretory cells of the PI. mutant virgin adults of both sexes have a significantly shorter lifespan than their parental strain. This longevity defect is completely reversed by mating (lifespan increases over 50% for males and females). Analyses of mutant mated adult brains revealed a complete rescue of dILP2 neurons without Drifter. Taken together, the data suggest that participates in a neural network connecting the insulin signaling pathway, longevity and mating. The conserved sequence and CNS specificity of all CORL proteins imply that this network may be operating in mammals.
CORL蛋白（在小鼠中称为SKOR，在人类中称为Fussel，在Flybase中称为fussel）是一类与Sno/Ski癌基因相关的中枢神经系统特异性蛋白。它们在发育和成年期的作用大多未知。一个果蝇（dCORL）报告基因在幼虫和成年果蝇大脑间脑（PI）的所有果蝇胰岛素样肽2（dILP2）神经元中表达。转录因子Drifter也在PI中表达，存在于一部分表达dCORL和dILP2的神经元以及一些非dILP2神经元中。突变的成年处女蝇大脑中缺失所有不表达Drifter的dILP2神经元。当在PI的神经分泌细胞中表达dCORL-RNAi时也会出现这种表型。突变的成年处女蝇无论雌雄，其寿命都比亲本品系显著缩短。这种寿命缺陷在交配后完全逆转（雌雄寿命均增加超过50%）。对突变的成年交配蝇大脑的分析显示，不表达Drifter的dILP2神经元完全得到了挽救。综合来看，这些数据表明，[基因名称]参与了一个连接胰岛素信号通路、寿命和交配的神经网络。所有CORL蛋白的保守序列和中枢神经系统特异性意味着这个网络可能在哺乳动物中发挥作用。
