Molecular mechanism underlying Strip-Hippo pathway regulates neural synapse formation

• Project/Area Number: 15H04375
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Hiroshima University (2016-2017); The University of Tokyo (2015)
• Principal Investigator: CHIHARA Takahiro 広島大学, 理学研究科, 教授 (00431891)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
• Keywords: 神経発生 / シナプス / Hippo / ショウジョウバエ / 神経 / 遺伝学

Outline of Final Research Achievements

In this study, we tried to reveal the molecular mechanism underlying hippo pathway regulates neural function. By using Drosophila genetic screen, we identified the evolutionarily conserved amino acid transporter, HiAT (Hippo-interacting Amino acid Transporter) as a regulator of hippo pathway in neuronal synapse formation. Furthermore, we found that HiAT and hippo kinase can affect animal locomotor activity.

Research Products

• [Int'l Joint Research] スタンフォード大学(米国)
• [Int'l Joint Research] クアラルンプール病因(マレーシア)
• [Int'l Joint Research] テルアビブ大学(イスラエル)
• [Int'l Joint Research] マックスプランク研究所(ドイツ)
• [Journal Article] Role of the STRIPAK complex and the Hippo pathway in synaptic terminal formation (2017)
  • Author(s): Chisako Sakuma and Takahiro Chihara
  • Journal Title: Neural Regeneration Research Volume: 12 Issue: 4 Pages: 578-579
  • DOI: 10.4103/1673-5374.205089
  • Peer Reviewed
• [Journal Article] Dendritic Eph organizes dendrodendritic segregation in discrete olfactory map formation in Drosophila (2017)
  • Author(s): Marie Anzo, Sayaka Sekine, Shirin Makihara, Kinhong Chao, Masayuki Miura and Takahiro Chihara
  • Journal Title: Genes and Development Volume: 31 Issue: 10 Pages: 1054-1065
  • DOI: 10.1101/gad.297424.117
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Biallelic TBCD mutations cause early-onset neurodegenerative encephalopathy (2017)
  • Author(s): Miyake N, Fukai R, Ohba C, ... Shiina M, Ogata K, Okuno-Yuguchi J, Fueki N, Ogiso Y, Suzumura H, Watabe Y, Imataka G, Leong HY, Fattal-Valevski A, Kramer U, Miyatake S, Kato M, Okamoto N, Sato Y, Mitsuhashi S, Nishino I, Kaneko N, Nishiyama A, Tamura T, Mizuguchi T, Nakashima M, Tanaka F, Saitsu H, Matsumoto N
  • Journal Title: American Journal of Human Genetics Volume: 99 Issue: 4 Pages: 950-961
  • DOI: 10.1016/j.ajhg.2016.08.005
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The Strip-Hippo Pathway Regulates Synaptic Terminal Formation by Modulating Actin Organization at the Drosophila Neuromuscular Synapses. (2016)
  • Author(s): Sakuma C, Saito Y, Umehara T, Kamimura K, Maeda N, Mosca TJ, Miura M, Chihara T.
  • Journal Title: Cell Rep Volume: 16 Issue: 9 Pages: 2289-2297
  • DOI: 10.1016/j.celrep.2016.07.066
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Familial Amyotrophic Lateral Sclerosis-linked Mutations in Profilin 1 Exacerbate TDP-43-induced Degeneration in the Retina of Drosophila melanogaster through an Increase in the Cytoplasmic Localization of TDP-43. (2016)
  • Author(s): Matsukawa K, Hashimoto T, Matsumoto T, Ihara R, Chihara T, Miura M, Wakabayashi T, Iwatsubo T.
  • Journal Title: J Biol Chem Volume: 291 Issue: 45 Pages: 23464-23476
  • DOI: 10.1074/jbc.m116.729152
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Function of pioneer neurons specified by the basic helix-loop-helix transcription factor atonal in neural development. (2016)
  • Author(s): Okumura M, Chihara T.
  • Journal Title: Neural Regen Res Volume: 11 Issue: 9 Pages: 1394-1395
  • DOI: 10.4103/1673-5374.191201
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Tissue non-autonomous effects of fat body methionine metabolism on imaginal disc repair in Drosophila. (2016)
  • Author(s): Kashio, S., Obata, F., Zhang, L., Katsuyama, T., Chihara, T., and Miura, M.
  • Journal Title: Proc. Natl. Acad. Sci. USA. Volume: 113 Issue: 7 Pages: 1835-1840
  • DOI: 10.1073/pnas.1523681113
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A STRIPAK component Strip regulates neuronal morphogenesis by affecting microtubule stability. (2015)
  • Author(s): Sakuma, C., Okumura, M., Umehara, T., Miura, M., and T. Chihara.
  • Journal Title: Sci. Rep. Volume: 5 Issue: 1 Pages: 17769-17769
  • DOI: 10.1038/srep17769
  • NAID: 120006800823
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hierarchical axon targeting of Drosophila olfactory receptor neurons specified by the proneural transcription factors Atonal and Amos (2015)
  • Author(s): Okumura, M., Kato, T., Miura, M. and Chihara, T.
  • Journal Title: Genes Cells Volume: 21 Issue: 1 Pages: 53-64
  • DOI: 10.1111/gtc.12321
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The roles of tubulin-folding cofactors in neuronal morphogenesis and disease (2015)
  • Author(s): Okumura, M., Miura, M. and Chihara, T.
  • Journal Title: Neural Regeneration Research Volume: 10 Issue: 9 Pages: 1388-1389
  • DOI: 10.4103/1673-5374.165226
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] An ER-resident nucleotide sugar transporter, Meigo regulates dendrite targeting specificity in Drosophila olfactory circuit. (2015)
  • Author(s): Chihara, T., Sekine, S., Moriya, M. and Miura, M.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸国際会議場、神戸
  • Year and Date: 2015-07-28
  • Invited