Analysis of ciliary protein complex that determines renal cyst developments

决定肾囊肿发展的纤毛蛋白复合物分析

• 批准号: 24790198
• 负责人: SHIBA DAI
• 金额: $ 2.91万
• 依托单位: Japan Aerospace Exploration Agency (2013)Kyoto Prefectural University of Medicine (2012)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24790198/
• 关键词: 一次繊毛; 腎臓; 嚢胞; メカノストレス; 前庭機能; シグナル伝達; 繊毛; 分子構造; 生体応答; 核移行

Primary cilia have diverse functions in cell signaling pathways, including mechanosensation and hedgehog signaling. More than 1000 proteins are now identified to localize in the cilium. Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease. Among 12 reported Nphp gene products, Inv/Nphp2 and Nek8/Nphp9 are localized to the proximal segment in the primary cilium. However, the functional relationships are unknown. This study focused on phenotype analysis of nek8 knockdown embryos and the genetic relationship between nek8 and inv in zebrafish. Knockdown of nek8 produced pronephric cysts. Simultaneous knockdown of nek8 and inv synergistically increased the incidence of these defects. Interestingly, nek8 mRNA rescued inv morphant phenotypes, although inv mRNA could not rescue nek8 morphant phenotypes. These results suggest that Nek8 acts downstream of Inv function.

初级纤毛在细胞信号通路中具有多种功能，包括机械感觉和刺猬信号。现在已经确定有超过1000种蛋白质定位于纤毛。肾病（NPHP）是一种常染色体隐性遗传性囊性肾病。在已报道的12个Nphp基因产物中，Inv/Nphp2和Nek8/Nphp9定位于初级纤毛的近端。然而，功能关系尚不清楚。本研究主要对斑马鱼nek8基因敲除胚胎的表型分析以及nek8基因与inv基因的遗传关系进行了研究。敲低nek8产生肾原囊肿。同时敲低nek8和不协同增加这些缺陷的发生率。有趣的是，虽然inv mRNA不能挽救nek8的表型，但nek8 mRNA挽救了inv的表型。这些结果表明Nek8作用于Inv功能的下游。

项目成果

An attempt to isolate novel ciliary genes using whole mount in situ hybridization expression database

利用整体原位杂交表达数据库分离新的纤毛基因的尝试

• 发表时间: 2013
• 作者: 芝大;福井一;横山尚彦;小林大介,芝大,横山尚彦
• 通讯作者: 小林大介,芝大,横山尚彦

A three step process of Nphp3 ciliary localization

Nphp3 纤毛定位的三步过程

• 发表时间: 2013
• 作者: Shiba D;Nakata K;Fukui H;Kobayashi D and Yokoyama T
• 通讯作者: Kobayashi D and Yokoyama T

The ciliary protein Nek8/Nphp9 acts downstream of Inv/Nphp2

纤毛蛋白 Nek8/Nphp9 作用于 Inv/Nphp2 下游

• 发表时间: 2013
• 作者: 芝大;福井一;横山尚彦
• 通讯作者: 横山尚彦

宇宙マウスにかける夢

梦见太空鼠的相关梦境

• 发表时间: 2014
• 期刊: 生物工学会誌
• 作者: 塚田岳大;藤原 研;Dini Ramadhani;矢田部恵;屋代 隆;芝 大
• 通讯作者: 芝 大

Deficiency of NOX1/Nicotinamide Adenine Dinucleotide Phosphate, Reduced Form Oxidase Leads to Pulmonary Vascular Remodeling

• DOI: 10.1161/atvbaha.113.302107
• 发表时间: 2014-01-01
• 期刊: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
• 影响因子: 8.7
• 作者: Iwata, Kazumi;Ikami, Kanako;Yabe-Nishimura, Chihiro
• 通讯作者: Yabe-Nishimura, Chihiro