The role of protein glycosylation in the regulation of Ephrin/Eph signal

• Project/Area Number: 23687032
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Developmental biology
• Research Institution: The University of Tokyo
• Principal Investigator: CHIHARA Takahiro 東京大学, 薬学研究科(研究院), 准教授 (00431891)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥27,040,000 (Direct Cost: ¥20,800,000、Indirect Cost: ¥6,240,000); Fiscal Year 2014: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2013: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2012: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
• Keywords: Eph / Ephrin / 神経 / 発生 / 糖鎖修飾 / ショウジョウバエ / 遺伝学 / 樹状突起 / 神経回路 / 小胞体 / 糖鎖

Outline of Final Research Achievements

An evolutionarily conserved signal, Ephrin/Eph signal functions in axon guidance, blood vessel formation and body segmentation etc. In this study, we aimed to reveal the regulatory mechanism of Ephrin/Eph signal by using biochemical methods and Drosophila genetics. We succeeded to show the significance of Ephrin N-glycosylation for its stability and subcellular localization, which is essential for proper Ephrin/Eph signal in neural development.

Research Products

• [Journal Article] Linking Cell Surface Receptors to Microtubules: Tubulin Folding Cofactor D Mediates Dscam Functions during Neuronal Morphogenesis (2015)
  • Author(s): Misako Okumura, Chisako Sakuma, Masayuki Miura, Takahiro Chihara
  • Journal Title: Journal of Neuroscience Volume: 35 Issue: 5 Pages: 1979-1990
  • DOI: 10.1523/jneurosci.0973-14.2015
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A stripak component Strip serves as a platform for early endosome organization during axon elongation. (2014)
  • Author(s): Sakuma, C., Kawauchi, T., Haraguchi, S., Shikanai, M., Yamaguchi, Y., Gelfand, V.I., Luo, L., Miura, M., and Chihara, T.
  • Journal Title: Nature Comm. Volume: 5 Issue: 1 Pages: 5180-5180
  • DOI: 10.1038/ncomms6180
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Caspase inhibition in select olfactory neurons restores innate attraction behavior in aged Drosophila. (2014)
  • Author(s): Chihara, T., Kitabayashi, A., Morimoto, M., Takeuchi, K., Masuyama, K., Tonoki, A., Davis, R.L., Wang, J.W., and Miura, M.
  • Journal Title: PLOS Genetics Volume: 10 Issue: 6 Pages: e1004437-e1004437
  • DOI: 10.1371/journal.pgen.1004437
  • NAID: 120006799366
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Development of olfactory projection neuron dendrites that contribute to wiring specificity of the Drosophila olfactory circuit (2014)
  • Author(s): Chisako Sakuma, Marie Anzo, Masayuki Miura and Takahiro Chihara
  • Journal Title: Genes and Genetic Systems Volume: 89 Pages: 17-26
  • NAID: 130004137818
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Meigo governs dendrite targeting specificity by modulating Ephrin level and N-glycosylation. (2013)
  • Author(s): Sekine, S.U., Haraguchi. S., Chao, K., Kato, T., Luo, L., Miura, M., and Chihara, T.
  • Journal Title: Nature Neuro Sci. Volume: 16 Issue: 6 Pages: 683-691
  • DOI: 10.1038/nn.3389
  • Peer Reviewed
• [Journal Article] RNA binding mediates neurotoxicity in the transgenic Drosophila model of TDP-43 proteinopathy. (2013)
  • Author(s): Ihara R, Matsukawa K, Nagata Y, Kunugi H, Tsuji S, Chihara T, Kuranaga E, Miura M, Wakabayashi T, Hashimoto T, Iwatsubo T.
  • Journal Title: Hum Mol Genet. Volume: 22(22) Issue: 22 Pages: 4474-4484
  • DOI: 10.1093/hmg/ddt296
  • Peer Reviewed
• [Journal Article] Prevention of apoptosis by mitochondrial phosphatase PGAM5 in the mushroom body is crucial for heat shock resistance in Drosophila melanogaster (2012)
  • Author(s): Ishida Y, Sekine Y, Oguchi H, Chihara T, Miura M, Ichijo H, Takeda K
  • Journal Title: PLoS One Volume: 7
  • Peer Reviewed
• [Presentation] Hippo and its negative regulator Strip regulate synapse formation at Drosophila larval neuromuscular junctions (2015)
  • Author(s): Takahiro Chihara, Chisako Sakuma, Yoshie Saito, Tomoki Umehara, Keisuke Kamimura, Timothy Mosca, Nobuyuki Meda and Masayuki Miura
  • Organizer: 56th Annual Drosophila Research Conference
  • Place of Presentation: Chicago, USA
  • Year and Date: 2015-03-04 – 2015-03-08
• [Presentation] Molecular and cellular mechanism underlying neural map formation in Drosophila (2015)
  • Author(s): Takahiro Chihara
  • Organizer: Global COE Liaison Laboratory Seminar
  • Place of Presentation: 熊本大学
  • Year and Date: 2015-01-28
  • Invited
• [Presentation] 神経発生において特異的な機能を持つ小胞 体分子Meigo (2014)
  • Author(s): 千原崇裕、関根清薫、森谷浩幸、三浦正幸
  • Organizer: 第87回生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15 – 2014-10-18
  • Invited
• [Presentation] Dogi serves as a platform for early endosome organization during axon elongation (2014)
  • Author(s): Chisako Sakuma, Takeshi Kawauchi, Shuka Haraguchi, Mima Shikanai, Yoshifumi Yamaguchi, Vladimir Gelfand, Liqun Luo, Masayuki Miura and Takahiro Chihara
  • Organizer: The 37th annual meeting of the Japan neuroscience society
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Novel function of Hippo: Hpo and its negative regulator Dogi regulate synapse formation at Drosophila larval neuromuscular junctions (2014)
  • Author(s): Chisako Sakuma, Yoshie Saito, Tomoki Umehara, Keisuke Kamimura, Timothy Mosca, Nobuyuki Meda, Masayuki Miura and Takahiro Chihara
  • Organizer: Japanese Drosophila Research Conference 11
  • Place of Presentation: 金沢
  • Year and Date: 2014-06-04 – 2014-06-06
• [Presentation] Tubulin folding cofactor D regulates neuronal morphogenesis by mediating Dscam functions. (2014)
  • Author(s): Misako Okumura, Chisako Sakuma, Masayuki Miura and Takahiro Chihara
  • Organizer: Japanese Drosophila Research Conference 11
  • Place of Presentation: 金沢
  • Year and Date: 2014-06-04
• [Presentation] Endoplasmic reticulum protein, Meigo, controls dendrite and axon targeting along a specific axis in the Drosophila olfactory map (2013)
  • Author(s): Sayaka Sekine, Liqun Luo, Masayuki Miura and Takahirio Chihara
  • Organizer: 2nd Asia-Pacific Drosophila Research Conference
  • Place of Presentation: Seoul, Korea
• [Presentation] Age-dependent apoptosis of select olfactory neurons impairs innate attraction behavior in Drosophila (2013)
  • Author(s): Takahiro Chihara, Aki Kitabayashi, Michie Morimoto, Ken-ichi Takeuchi, Kaoru Masuyama, Ayako Tonoki, Ronald L. Davis, Jing W. Wang and Masayuki Miura
  • Organizer: 第４６回日本発生生物学会年会
  • Place of Presentation: 松江、島根
• [Presentation] Role of tubulin folding pathway in neurite morphogenesis of Drosophila olfactory projection neuron (2013)
  • Author(s): Misako Okumura, Masayuki Miura and Takahiro Chihara
  • Organizer: 第４６回日本発生生物学会年会
  • Place of Presentation: 松江、島根
• [Presentation] In vivo model system to study the genetic program of tissue regeneration (2013)
  • Author(s): Soshiro Kashio, Fumiaki Obata1, Liu Zhang, Takahiro Chihara and Masayuki Miura
  • Organizer: 第４６回日本発生生物学会年会
  • Place of Presentation: 松江、島根
• [Presentation] Unveiling the role of Ephrin for dendrite targeting of Drosophila olfactory projection neurons (2013)
  • Author(s): Shirin Makihara, Sayaka Sekine, Masayuki Miura and Takahiro Chihara
  • Organizer: 第４６回日本発生生物学会年会
  • Place of Presentation: 松江、島根
• [Presentation] Dogi: an essential factor for early endosome maturation and the tumor suppressor Hippo signal in developing neurons (2013)
  • Author(s): Takahiro Chihara, Chisako Sakuma, Yoshie Saito, Takeshi Kawauchi, Shuka Haraguchi, Mima Shikanai, Yoshifumi Yamaguchi, Vladimir I. Gelfand, Liqun Luo and Masayuki Miura
  • Organizer: 第６５回日本細胞生物学会大会
  • Place of Presentation: 名古屋、愛知
  • Invited
• [Presentation] Dogi: an essential factor for early endosome maturation and the tumor suppressor Hippo signal in developing neurons (2013)
  • Author(s): Chisako Sakuma, Yoshie Saito, Takeshi Kawauchi, Shuka Haraguchi, Mima Shikanai, Yoshifumi Yamaguchi, Vladimir I. Gelfand, Liqun Luo, Masayuki Miura and Takahiro Chihara
  • Organizer: 第８６回日本生化学会大会
  • Place of Presentation: 横浜、神奈川
  • Invited
• [Presentation] 神経回路の一生を支える分子基盤、ショウジョウバエ遺伝学を用いたアプローチ (2013)
  • Author(s): 千原 崇裕
  • Organizer: 熊本大学 発生医学研究所 発生研セミナー
  • Place of Presentation: 熊本、熊本
  • Invited
• [Presentation] APOPTOSIS OF SELECT OLFACTORY NEURONS CAUSES AGEDEPENDENT IMPAIRMENT OF INNATE ATTRACTION BEHAVIOR IN DROSOPHILA (2013)
  • Author(s): Takahiro Chihara, Aki Kitabayashi, Michie Morimoto, Ken-ichiTakeuchi, Kaoru Masuyama, Ayako Tonoki, Ronald L Davis4, Jing W Wang and Masayuki Miura
  • Organizer: Neurobiology of Drosophila, Cold Spring Harbor Meeting
  • Place of Presentation: New York, USA
• [Presentation] NEURONAL MORPHOGENESIS REQUIRES DOGI, A NOVELREGULATOR OF EARLY ENDOSOME ORGANIZATION (2013)
  • Author(s): Chisako Sakuma, Vladimir I Gelfand, Liqun Luo, Masayuki Miura and Takahiro Chihara
  • Organizer: Neurobiology of Drosophila, Cold Spring Harbor Meeting
  • Place of Presentation: New York, USA
• [Presentation] Neurite branching and elongation are regulated by Dogi, a novel microtubule interacting protein (2012)
  • Author(s): Chisako Sakuma
  • Organizer: 14th European Drosophila Neurobiology Conference
  • Place of Presentation: Padua, Italy
• [Presentation] Nucleotide sugar transporter Meigo regulates both dendrite and axon targeting of synaptic partners through Ephrin signaling in the olfactory system (2012)
  • Author(s): Sekine, S., Liang, L., Hino-Yamamoto, M., Goto, S., Okano, H., Luo, L., Miura, M., Chihara, T
  • Organizer: 53rd Annual Drosophila Research Conference
  • Place of Presentation: Chicago, USA
• [Presentation] Evolutionarily conserved protein Dogi is required for neurite branching and targeting by interacting with microtubule motor regulator Glued in Drophila olfactory projection neurons (2011)
  • Author(s): Sakuma, C., Luo, L., Miura, M., Chihara, T.
  • Organizer: 44th Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: 京都
• [Presentation] Neuronal targeting of synaptic partners are regulated by cell-autonomous function of Meigo, a putative UDP-sugar transporter, in the Drosophila olfactory brain center (2011)
  • Author(s): Sekine, S., Luo, L., Miura, M., Chihara, T
  • Organizer: 44^<th> Annual meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: Okinawa, Japan
• [Presentation] Evolutionarily Conserved Protein Dogi Regulates Neurite Targeting in the Olfactory System (2011)
  • Author(s): Sakuma, C., Luo, L., Miura, M., Chihara, T.
  • Organizer: 1^<st> Asia-Pacific Drosophila Research Conference
  • Place of Presentation: Taipei, Taiwan
• [Presentation] Nucleotide sugar transporter Meigo regulates neuronal targeting of synaptic partners in the Drosophila antennal lobe (2011)
  • Author(s): Sekine, S., Luo, L., Miura, M., Chihara, T
  • Organizer: 1^<st> Asia-Pacific Drosophila Research Conference
  • Place of Presentation: Taipei, Taiwan
• [Presentation] Nucleotide sugar transporter Meigo is required for neuronal targeting of synaptic partners in the Drosophila antennal lobe (2011)
  • Author(s): Sekine, S., Hino, M., Goto, S., Okano, H., Luo, L., Miura, M., Chihara, T
  • Organizer: Cold Spring Harbor Laboratory Meeting, NEROBI OLOGY OF DROSOPHILA
  • Place of Presentation: New York, USA
• [Presentation] ER homeostasis and vesicle trafficking for the olfactory wiring specificity in Drosophila
  • Author(s): Takahiro Chihara
  • Organizer: 45rd Annual meeting for the Japanese society of developmental biologists & The 64th annual meeting of the Japan society for cell society
  • Place of Presentation: Kobe
  • Invited