Analysis of ciliary protein complex that determines renal cyst developments

• Project/Area Number: 24790198
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Japan Aerospace Exploration Agency (2013); Kyoto Prefectural University of Medicine (2012)
• Principal Investigator: SHIBA DAI 独立行政法人宇宙航空研究開発機構, 有人宇宙ミッション本部, 主任研究員 (50360722)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 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

Research Abstract

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.

Research Products

• [Journal Article] Deficiency of NOX1/nicotinamide adenine dinucleotide phosphate, reduced form oxidase leads to pulmonary vascular remodeling (2014)
  • Author(s): Iwata K, Ikami K, Matsuno K, Yamashita T, Shiba D, Ibi M, Matsumoto M, Katsuyama M, Cui W, Zhang J, Zhu K, Takei N, Kokai Y, Ohneda O, Yokoyama T, Yabe-Nishimura C
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: 34(1) Pages: 110-9
• [Journal Article] Deficiency of NOX1/nicotinamide adenine dinucleotide phosphate, reduced form oxidase leads to pulmonary vascular remodeling. (2014)
  • Author(s): Iwata K, Ikami K, Matsuno K, Yamashita T, Shiba D, Ibi M, Matsumoto M, Katsuyama M, Cui W, Zhang J, Zhu K, Takei N, Kokai Y, Ohneda O, Yokoyama T, Yabe-Nishimura C.
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: 34(1) Issue: 1 Pages: 110-119
  • DOI: 10.1161/atvbaha.113.302107
  • Peer Reviewed
• [Journal Article] 宇宙マウスにかける夢 (2014)
  • Author(s): 芝 大
  • Journal Title: 生物工学会誌 Volume: 第92巻1号 Pages: 44-44
• [Journal Article] The ciliary protein Nek8/Nphp9 acts downstream of Inv/Nphp2 during pronephros morphogenesis and left-right establishment in zebrafish (2012)
  • Author(s): Fukui H, Shiba D, Asakawa K, Kawakami K and Yokoyama T
  • Journal Title: FEBS Lett. Volume: 586(16) Pages: 2273-9
• [Journal Article] The ciliary protein Nek8/Nphp9 acts downstream of Inv/Nphp2 during pronephros morphogenesis and left-right establishment in zebrafish. (2012)
  • Author(s): Fukui H, Shiba D, Asakawa K, Kawakami K and Yokoyama T.
  • Journal Title: FEBS Lett. Volume: 586(16) Pages: 2273-2279
  • Peer Reviewed
• [Presentation] The ciliary protein Nek8/Nphp9 acts downstream of Inv/Nphp2 (2013)
  • Author(s): 芝大、福井一、横山尚彦
  • Organizer: 第118回日本解剖学会総会・全国学術集会
  • Place of Presentation: 香川
• [Presentation] An attempt to isolate novel ciliary genes using whole mount in situ hybridization expression database (2013)
  • Author(s): 小林大介,芝大,横山尚彦
  • Organizer: 第118回日本解剖学会総会・全国学術集会
  • Place of Presentation: 香川
• [Presentation] The ciliary protein Nek8/Nphp9 acts downstream of Inv/Nphp2 (2013)
  • Author(s): Shiba D, Fukui H and Yokoyama T.
  • Organizer: 第118回日本解剖学会
  • Place of Presentation: 香川
• [Presentation] A three-step process of Nphp3 ciliary localization (2012)
  • Author(s): Dai Shiba, Kana Nakata, Hajime Fukui, Daisuke Kobayashi and Takahiko Yokoyama
  • Organizer: CILIA 2012-1st International Scientific Conference
  • Place of Presentation: London(抄録CILIA 2012 Conference Book, 44)
• [Presentation] The ciliary protein Nek8/Nphp9 acts downstream of Inv/Nphp2 (2012)
  • Author(s): Dai Shiba, Hajime Fukui, Kazuhide Asakawa, Koichi Kawakam and Takahiko Yokoyama
  • Organizer: The American Society for Cell Biology Annual Meeting
  • Place of Presentation: The Moscone Center, San Francisco, CA(抄録The American Society for Cell Biology, Annual Meeting Program, L9)