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Suppression of Patronin deficiency by altered Hippo signaling in Drosophila organ development.
Cell Death and Differentiation ( IF 12.4 ) Pub Date : 2020-07-31 , DOI: 10.1038/s41418-020-0597-x
Dae-Wook Yang 1 , Kwang-Wook Choi 1
Affiliation  

The microtubule network is crucial for cell structure and function. Patronin is a conserved protein involved in protecting the minus end of microtubules. Conversely, Klp10A is a kinesin-like microtubule depolymerase. Here we report the role of Drosophila Patronin and Klp10A for cell survival in developing organs. Loss of Patronin reduces the size of organs by activation of a caspase in imaginal discs. Reduced wing by Patronin RNAi is suppressed by knockdown of Spastin (Spas) but not Katanin 60, suggesting that Patronin is inhibitory to the severing function of Spas at the minus end. Patronin RNAi phenotype is also recovered by overexpressing Death-associated inhibitor of apoptosis 1 (Diap1), a Yorkie target gene. Heterozygote mutations in Hippo pathway genes, including hippo and warts (wts), suppress the Patronin RNAi wing phenotypes. Furthermore, Patronin physically interacts with Merlin and Expanded while reducing their function. Patronin and Klp10A antagonistically regulate their levels. Wing phenotypes of Patronin RNAi are rescued by knockdown of Klp10A, consistent with their antagonistic interaction. Klp10A overexpression also causes organ size reduction that is partially suppressed by Diap1 overexpression or wts heterozygote mutation. Taken together, this study suggests that the antagonistic interaction between Patronin and Klp10A is required for controlling cell survival and organ size by modulating microtubule stability and Hippo components.



中文翻译:

在果蝇器官发育中通过改变 Hippo 信号抑制 Patronin 缺乏症。

微管网络对细胞结构和功能至关重要。Patronin 是一种保守的蛋白质,参与保护微管的负端。相反,Klp10A 是一种驱动蛋白样微管解聚酶。在这里,我们报告了果蝇Patronin 和 Klp10A 在发育器官中的细胞存活中的作用。Patronin 的缺失通过激活成虫盘中的半胱天冬酶来减小器官的大小。由Patronin RNAi 引起的翅膀减少被Spastin (Spas) 的敲低所抑制,但 Katanin 60 不会,这表明 Patronin 在负端抑制 Spas 的切断功能。Patronin RNAi表型也通过过表达死亡相关细胞凋亡抑制剂 1 ( Diap1),一个 Yorkie 目标基因。Hippo 通路基因中的杂合子突变,包括河马( wts ),抑制了Patronin RNAi翼表型。此外,Patronin 与 Merlin 和 Expanded 进行物理交互,同时降低它们的功能。Patronin 和 Klp10A 拮抗调节它们的水平。Patronin RNAi 的翼表型通过Klp10A的敲低来拯救,这与它们的拮抗相互作用一致。Klp10A 过表达也会导致器官大小减少,这部分被 Diap1 过表达或wts抑制杂合子突变。总之,这项研究表明,通过调节微管稳定性和 Hippo 成分来控制细胞存活和器官大小需要 Patronin 和 Klp10A 之间的拮抗相互作用。

更新日期:2020-07-31
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