分成三部分的主题(修剪) 家庭蛋白质是戒指手指包含域,多域蛋白质在许多生物过程含有。包括 TRIM-9, MID1 和 MID2,整齐的蛋白质的 TRIM-9/C-I 亚科的成员有 neuronal 功能并且与神经病学的疾病被联系。为了探索 C-I 的功能是否整修蛋白质,在无脊椎动物被保存,我们分析了 Caenorhabditis elegans 和果蝇 trim-9 异种。C。elegans trim-9 异种在雌雄同体的腹的指导展出缺点特定的神经原(HSN ) 和触摸神经原 AVM。进一步基因的分析显示 TRIM-9 参予 UNC-6-UNC-40 吸引力小径。UNC-40 的不对称的分发在 trim-9 异种在 HSN 开发期间是正常的。然而, MIG-10 的不对称的本地化, UNC-40 的一个下游的受动器,在 trim-9 异种被废除。这些结果建议 TRIM-9 工作在 UNC-40 小径的 MIG-10 在上游。而且,我们证明在 vitro 的 TRIM-9 展览 E3 ubiquitin ligase 活动和这项活动为在 vivo 的 TRIM-9 功能是重要的。另外,我们发现果蝇 trim-9 为一组感觉神经原轴突的中线吸引力被要求。Netrin/UNC-6 受体的在表示上穿破在 trim-9 异种压制指导缺点。我们的学习在 UNC-40/Frazzled-mediated UNC-6/Netrin 吸引力小径揭示 TRIM-9 的 evolutionarily 保存的功能。
TRIpartite Motif (TRIM) family proteins are ring finger domain-containing, multi-domain proteins implicated in many biological processes. Members of the TRIM-9/C-I subfamily of TRIM proteins, including TRIM-9, MIDI and MID2, have neuronal functions and are associated with neurological diseases. To explore whether the functions of C-I TRIM proteins are conserved in invertebrates, we analyzed Caenorhabditis elegans and Drosophila trim-9 mutants. C. elegans trim-9 mutants exhibit defects in the ventral guidance of hermaphrodite specific neuron (HSN) and the touch neuron AVM. Further genetic analyses indicate that TRIM-9 participates in the UNC-6-UNC-40 attraction pathway. Asymmetric distribution of UNC-40 during HSN development is normal in trim-9 mutants. However, the asymmetric localization of MIG-10, a downstream effector of UNC-40, is abolished in trim-9 mutants. These results suggest that TRIM-9 functions upstream of MIG- 10 in the UNC- 40 pathway. Moreover, we showed that TRIM-9 exhibits E3 ubiquitin ligase activity in vitro and this activity is important for TRIM-9 function in vivo. Additionally, we found that Drosophila trim-9 is required for the midline attraction of a group of sensory neuron axons. Over-expression of the Netrin/UNC-6 receptor Frazzled suppresses the guidance defects in trim-9 mutants. Our study reveals an evolutionarily conserved function of TRIM-9 in the UNC-40/Frazzled-mediated UNC-6/Netrin attraction pathway.