Genome-wide analysis reveals novel regulators of synaptic maintenance in Drosophila.
Genome-wide analysis reveals novel regulators of synaptic maintenance in Drosophila.
复制标题
DOI：
10.1093/genetics/iyad025
复制
发表时间：
2023-04-06
期刊：
影响因子：
3.3
通讯作者：
Babcock, Daniel T.
中科院分区：
文献类型：
--
作者：
Sidisky, Jessica M.;Moreira, Danielle de Paula;Okumus, Meryem;Caratenuto, Russell;Drost, Cassidy;Connors, Bali;Hussain, Sarrah;Alkhatib, Stephanie;Babcock, Daniel T.
保持突触通讯是保持神经系统功能所必需的，因为有机体的年龄。虽然已经完成了许多工作来了解突触的形成和发育，但我们对在整个衰老过程中保持突触完整性的了解相对较少。为了更好地了解负责维持突触结构和功能的机制，我们进行了无偏的遗传筛选，以确定成年果蝇神经肌肉接头突触维持所需的基因。使用飞行行为作为筛选工具，我们评估了果蝇遗传参考小组的198个品系的飞行能力，以确定单核苷酸多态性（SNP）与飞行能力随年龄的进行性丧失相关。在从这个屏幕上确定的许多候选基因中，我们在这里集中在10个基因与明确的人类同源物窝藏SNPs是最高度相关的突触维护。这些基因突变等位基因的功能验证揭示了突触结构完整性的逐步丧失。使用RNA干扰（RNAi）对这些基因进行组织特异性敲除，揭示了这些基因在突触前运动神经元、突触后肌肉或相关神经胶质细胞中的重要作用，突出了三重突触每个组成部分的重要性。这些结果提供了更深入的了解负责保持突触的结构和功能的完整性与年龄的机制。
Maintaining synaptic communication is required to preserve nervous system function as an organism ages. While much work has been accomplished to understand synapse formation and development, we understand relatively little regarding maintaining synaptic integrity throughout aging. To better understand the mechanisms responsible for maintaining synaptic structure and function, we performed an unbiased forward genetic screen to identify genes required for synapse maintenance of adult Drosophila neuromuscular junctions. Using flight behavior as a screening tool, we evaluated flight ability in 198 lines from the Drosophila Genetic Reference Panel to identify single nucleotide polymorphisms (SNPs) that are associated with a progressive loss of flight ability with age. Among the many candidate genes identified from this screen, we focus here on 10 genes with clear human homologs harboring SNPs that are most highly associated with synaptic maintenance. Functional validation of these genes using mutant alleles revealed a progressive loss of synaptic structural integrity. Tissue-specific knockdown of these genes using RNA interference (RNAi) uncovered important roles for these genes in either presynaptic motor neurons, postsynaptic muscles, or associated glial cells, highlighting the importance of each component of tripartite synapses. These results offer greater insight into the mechanisms responsible for maintaining structural and functional integrity of synapses with age.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.3
作者：
Davis J;Da Silva Santos C;Zavala NC;Gans N;Patracuolla D;Fehrenbach M;Babcock DT
通讯作者：
Babcock DT
影响因子：
1.2
作者：
Babcock, Daniel T.;Ganetzky, Barry
通讯作者：
Ganetzky, Barry
DOI：
10.1523/jneurosci.1015-11.2011
发表时间：
2011-06-01
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Buttermore ED;Dupree JL;Cheng J;An X;Tessarollo L;Bhat MA
通讯作者：
Bhat MA
影响因子：
3.7
作者：
Cifuentes-Diaz C;Chareyre F;Garcia M;Devaux J;Carnaud M;Levasseur G;Niwa-Kawakita M;Harroch S;Girault JA;Giovannini M;Goutebroze L
通讯作者：
Goutebroze L