Characterization of WNK signaling in development

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390064
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: HIROSHI Shibuya 東京医科歯科大学, 難治疾患研究所, 教授 (30261324)
• Co-Investigator(Renkei-kenkyūsha): SATO Atsushi 東京医科歯科大学, 難治疾患研究所, 助教 (30451925) ; GOTO Toshiyasu 東京医科歯科大学, 難治疾患研究所, 准教授 (00517518)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: WNK / PHAII / ショウジョウバエ / Lhx8/Awh / 細胞内シグナル / 神経分化 / 標的遺伝子

Research Abstract

WNK kinase family is conserved among many species and regulates SPAK/OSR1 and ion co-transporters. Some mutations in human WNK1 or WNK4 are associated with Pseudohypoaldosteronism type II, a form of hypertension. Here, we identify a new target gene in WNK signaling, Arrowhead and Lhx8, which is a mammalian homologue of Drosophila Arrowhead. In Drosophila, WNK was shown to genetically interact with Arrowhead. In Wnk1 knockout mice, levels of Lhx8 expression were reduced. Ectopic expression of WNK1, WNK4 or Osr1 in mammalian cells induced the expression of the Lhx8. Moreover, neural specification was inhibited by the knockdown of both Wnk1 and Wnk4 or Lhx8. Drosophila WNK mutant caused defects in axon guidance during embryogenesis. These results suggest that WNK signaling is involved in the morphological and neural development via Lhx8/Arrowhead.

Research Products

• [Journal Article] IQGAP1 protein regulates nuclear localization of ・ -catenin via importin- ・ 5 in Wnt signaling (2013)
  • Author(s): Goto, T., Sato, A., Shimizu, M., Adachi, S., Satoh, K., Iemura, S., Natsume, T. and Shibuya, H
  • Journal Title: J Biol Chem Volume: 288 Pages: 36351-36360
  • Peer Reviewed
• [Journal Article] WNK Signaling Is Involved in Neural Development via Lhx8/Awh Expression (2013)
  • Author(s): Sato, A. and Shibuya, H
  • Journal Title: PLoS One Volume: 8 Pages: e55301
  • DOI: 10.1371/journal.pone.0055301
  • Peer Reviewed
• [Journal Article] WNK4 is an essential effector of anterior formation in FGF signaling (2013)
  • Author(s): Shimizu, M., Goto, T., Sato, A. and Shibuya, H
  • Journal Title: Genes Cells Volume: 18 Pages: 442-449
  • DOI: 10.1111/gtc.12048
  • Peer Reviewed
• [Journal Article] IQGAP1 functions as a modulator of Dishevelled nuclear localization in Wnt signaling (2013)
  • Author(s): Goto, T., Sato, A., Shimizu, M., Adachi, S., Satoh, K., Iemura, S., Natsume, T. and Shibuya, H
  • Journal Title: PLoS One Volume: 8 Pages: e60865
  • DOI: 10.1371/journal.pone.0060865
  • Peer Reviewed
• [Journal Article] Leucine-rich repeat kinase LRRK1 regulates endosomal trafficking of the EGF receptor (2011)
  • Author(s): Hanafusa, H., Ishikawa, K., Kedashiro, S., Saigo, T., Iemura, S., Natsume, T., Komada, M., Shibuya, H., Nara, A. and Matsumoto, K.
  • Journal Title: Nat Commun Volume: 2 Pages: 158
  • Peer Reviewed
• [Presentation] IQGAP1 に よ るβ-catenin の核内移行の調節機構の解析 (2013)
  • Author(s): 後藤利保,佐藤淳,足立俊吾,家村俊一郎,夏目徹, 澁谷浩司
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸,ポスター発表
  • Year and Date: 20131200
• [Presentation] Wnt シグナルにおける DVL とβ -catenin の核移行制御 (2013)
  • Author(s): 澁谷浩司
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜,シンポジウム
  • Year and Date: 20130900
• [Presentation] A new downstream molecule, Awh is involved in the WNK signaling (2012)
  • Author(s): 佐藤淳,澁谷浩司
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡,口頭発表及びポスター発表
  • Year and Date: 20121200
• [Presentation] A new downstream molecule, Awh is involved in the WNK signaling (2011)
  • Author(s): 佐藤淳,澁谷浩司
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜,口頭発表及びポスター発表
  • Year and Date: 20111200
• [Remarks]
  • URL: http://www.tmd.ac.jp/mri/mri-mcb/index_j.html