Linking lysosomal trafficking defects with changes in aging and stress response in drosophila
Linking lysosomal trafficking defects with changes in aging and stress response in drosophila
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DOI：
10.4161/auto.4604
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发表时间：
2007-09-01
期刊：
影响因子：
13.3
通讯作者：
Finley, Kim D.
中科院分区：
文献类型：
--
作者：
Simonsen, Anne;Cumming, Robert C.;Finley, Kim D.
将细胞成分引导至溶酶体进行降解的途径的缺陷通常与活力下降和进行性疾病有关。此前我们已经证明，蓝纹奶酪（bchs：人类阿尔菲的果蝇同源物）突变会导致寿命缩短和泛素化神经聚集体的积累。基于眼睛中 Bchs 过度表达的遗传修饰筛选被用来识别几种潜在的遗传相互作用，其中包括自噬和内吞运输基因以及细胞骨架和运动蛋白以及 SUMO 和泛素信号通路的成员。我们发现，筛选中发现的几个基因的突变也会导致类似 bchs 的表型，包括成年寿命的缩短和泛素化蛋白质谱的变化。此外，我们发现属于自噬和跨高尔基体运输途径的 Bchs 修饰物也显示出成人饥饿反应的缺陷。我们的数据进一步支持 Bchs/Alfy 在外噬途径中的作用，并强烈表明自噬在衰老和应激反应中发挥着重要作用。
Defects in pathways that direct cellular components to the lysosome for degradation are often linked with a decrease in viability and with progressive disorders. Previously we had shown that blue cheese (bchs: Drosophila homologue of human Alfy) mutations lead to reduced longevity and the accumulation of ubiquitinated neural aggregates. A genetic modifier screen based on overexpression of Bchs in the eye was used to identify several potential genetic interactions, which included autophagic and endocytic trafficking genes as well as cytoskeletal and motor proteins and members of the SUMO and ubiquitin signaling pathways. We found that mutations in several of the genes identified in the screen also result in bchs-like phenotypes, including a reduction in adult lifespan and changes in ubiquitinated protein profiles. In addition, we show that Bchs modifiers belonging to the autophagic and trans-Golgi trafficking pathways also display defects in adult starvation response. Our data further support a role for Bchs/Alfy in the outophagic pathway and strongly indicate that autophagy plays an important role in aging and stress response.