Dimitriadou Agapi, Chatzianastasi Nasia, Zacharaki Panagiota I, O'Connor MaryJane, Goldsmith Samuel L, O'Connor Michael B, Consoulas Christos, Newfeld Stuart J
Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Dept. Genetics, Cell Biology & Development, University of Minnesota, Minneapolis, MN 55455.
G3 (Bethesda). 2020 May 4;10(5):1697-1706. doi: 10.1534/g3.120.400648.
The CORL family of CNS-specific proteins share a Smad-binding region with mammalian SnoN and c-Ski protooncogenes. In this family Drosophila CORL has two mouse and two human relatives. Roles for the mouse and human CORL proteins are largely unknown. Based on genome-wide association studies linking the human CORL proteins and with ataxia, we tested the hypothesis that mutations will cause adult movement disorders. For our initial tests, we conducted side by side studies of adults with the small deletion and eight control strains. We found that deletion mutants exhibit three types of behavioral plasticity. First, significant climbing defects attributable to loss of are eliminated by age. Second, significant phototaxis defects due to loss of are partially ameliorated by age and are not due to faulty photoreceptors. Third, males raised in groups have a lower courtship index than males raised as singles though this defect is not due to loss of Subsequent tests showed that the climbing and phototaxis defects were phenocpied by and two CRISPR generated mutations. Overall, the finding that adult movement defects due to loss of are subject to age-dependent plasticity suggests new hypotheses for CORL functions in flies and mammals.
中枢神经系统特异性蛋白的CORL家族与哺乳动物的SnoN和c-Ski原癌基因共享一个Smad结合区域。在这个家族中，果蝇CORL有两个小鼠和两个人类同源物。小鼠和人类CORL蛋白的作用在很大程度上尚不清楚。基于全基因组关联研究将人类CORL蛋白与共济失调联系起来，我们测试了突变会导致成人运动障碍的假设。对于我们的初步测试，我们对具有小缺失的成年果蝇和八个对照品系进行了并行研究。我们发现缺失突变体表现出三种行为可塑性类型。首先，由于[未提及基因名称]缺失导致的显著攀爬缺陷会随着年龄增长而消除。其次，由于[未提及基因名称]缺失导致的显著趋光性缺陷会随着年龄增长而部分改善，且不是由于光感受器故障。第三，群体饲养的雄性果蝇的求偶指数低于单独饲养的雄性果蝇，尽管这种缺陷不是由于[未提及基因名称]缺失。后续测试表明，攀爬和趋光性缺陷可由[未提及基因名称]和两个CRISPR产生的突变模拟。总体而言，由于[未提及基因名称]缺失导致的成年运动缺陷具有年龄依赖性可塑性这一发现，为果蝇和哺乳动物中CORL的功能提出了新的假设。
