Identification of a novel ADAMTS9 function for protein transport

• Project/Area Number: 25870759
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cell biology; General physiology
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Moizumi (Yoshina) Sawako 東京女子医科大学, 医学部, 助教 (00424672)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: ADAMTS9 / ２型糖尿病 / C.elegans / タンパク輸送 / 糖尿病

Outline of Final Research Achievements

It has been reported that an ADAMTS9 gene variant is associated with type 2 diabetes. The underlying pathology of type 2 diabetes is insulin resistance and beta-cell dysfunction. However, the molecular mechanisms underlying ADAMTS9 function in beta cells and peripheral tissues are unknown.
We investigated whether GON-1, the C.elegans homolog of ADAMTS9, is involved in the insulin secretion and insulin signaling in C.elegans. We found that both insulin secretion and the insulin-signaling pathway are compromised by GON-1 depletion. These defects in gon-1 mutants were restored by GON domain expression. These data suggest that the GON domain of GON-1 is involved in protein secretion from insulin secretory cells and in insulin/IGF-like signaling at peripheral tissues.

Research Products

• [Journal Article] Impaired NFKBIE gene function decreases cellular uptake of methotrexate by down-regulating SLC19A1 expression in a human rheumatoid arthritis cell line (2016)
  • Author(s): Imamura H, YoshinaS, Ikari K, Miyazawa K, Momohara S, Mitani S
  • Journal Title: Mod Rheumatol Volume: - Issue: 4 Pages: 1-10
  • DOI: 10.3109/14397595.2015.1112481
  • NAID: 120007144512
  • Peer Reviewed / Open Access
• [Journal Article] Curcumin improves tau-induced neuronal dysfunction of nematodes. (2016)
  • Author(s): Miyasaka, T., Xie, C., Yoshimura, S., Shinzaki, Y., Yoshina, S., Kage-Nakadai, E., Mitani, S., Ihara, Y.
  • Journal Title: Neurobiol. Aging Volume: 39 Pages: 69-81
  • DOI: 10.1016/j.neurobiolaging.2015.11.004
  • Peer Reviewed / Open Access
• [Journal Article] Locus-specific integration of extrachromosomal transgenes in C. elegans with the CRISPR/Cas9 system (2016)
  • Author(s): Yoshina et al.
  • Journal Title: BBRep Volume: 5 Pages: 70-76
  • DOI: 10.1016/j.bbrep.2015.11.017
  • Peer Reviewed / Open Access
• [Journal Article] Loss of C. elegans GON-1, an ADAMTS9 Homolog, Decreases Secretion Resulting in Altered Lifespan and Dauer Formation. (2015)
  • Author(s): Yoshina S, Mitani S
  • Journal Title: PLoS One Volume: 10 Issue: 7 Pages: e0133966-e0133966
  • DOI: 10.1371/journal.pone.0133966
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Longevity Genes Revealed by Integrative Analysis of Isoform-Specific daf-16/FoxO Mutants of Caenorhabditis elegans. (2015)
  • Author(s): Chen AT, Guo C, Itani OA, Budaitis BG, Williams TW, Hopkins CE, McEachin RC, Pande M, Grant AR, Yoshina S, Mitani S, Hu PJ.
  • Journal Title: Genetics Volume: 201 Issue: 2 Pages: 613-29
  • DOI: 10.1534/genetics.115.177998
  • Peer Reviewed / Open Access
• [Journal Article] The BED finger domain protein MIG-39 halts migration of distal tip cells in Caenorhabditis elegans. (2015)
  • Author(s): Kikuchi T, Shibata Y, Kim H.-S, Kubota Y, Yoshina S, Mitani S and Nishiwaki K
  • Journal Title: Dev. Biol. Volume: 397 Issue: 2 Pages: 151-161
  • DOI: 10.1016/j.ydbio.2014.10.008
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The Tumor Suppressor BCL7B Functions in the Wnt Signaling Pathway. (2015)
  • Author(s): Uehara T, Kage-Nakadai E, Yoshina S, Imae R, Mitani S.
  • Journal Title: PLoS Genet. Volume: 11 Issue: 1 Pages: e1004921-e1004921
  • DOI: 10.1371/journal.pgen.1004921
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] RNAi screening of human glycogene orthologs in the nematode Caenorhabditis elegans and the construction of the C. elegans glycogene database. (2014)
  • Author(s): Akiyoshi S, Nomura KH, Dejima K, Murata D, Matsuda A, Kanaki N, Takaki T, Mihara H, Nagaishi T, Furukawa S, Ando KG, Yoshina S, Mitani S, Togayachi A, Suzuki Y, Shikanai T, Narimatsu H, Nomura K.
  • Journal Title: Glycobiology Volume: 25(1) Issue: 1 Pages: 8-20
  • DOI: 10.1093/glycob/cwu080
  • Peer Reviewed / Open Access
• [Journal Article] PI3P phosphatase activity is required for autophagosome maturation and autolysosome formation. (2014)
  • Author(s): Wu Y, Cheng S, Zhao H, Zou W, Yoshina S, Mitani S, Zhang H, Wang X.
  • Journal Title: EMBO Rep. Volume: 15 Issue: 9 Pages: 973-81
  • DOI: 10.15252/embr.201438618
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A Conditional Knockout Toolkit for Caenorhabditis elegans Based on the Cre/loxP Recombination. (2014)
  • Author(s): Kage-Nakadai E, Imae R, Suehiro Y, Yoshina S, Hori S, Mitani S.
  • Journal Title: PLoS One. Volume: 9 Issue: 12 Pages: e114680-e114680
  • DOI: 10.1371/journal.pone.0114680
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Methods for single/low-copy integration by ultraviolet and trimethylpsoralen treatment in Caenorhabditis elegans. (2014)
  • Author(s): Kage-Nakadai E, Imae R, Yoshina S, Mitani S
  • Journal Title: Methods Volume: Mar 12 Issue: 3 Pages: 91-7
  • DOI: 10.1016/j.ymeth.2014.02.036
  • Peer Reviewed / Open Access
• [Journal Article] The homologous carboxyl-terminal domains of microtubule-associated protein 2 and TAU induce neuronal dysfunction and have differential fates in the evolution of neurofibrillary tangles. (2014)
  • Author(s): Xie, C., T. Miyasaka, S. Yoshimura, H. Hatsuta, S. Yoshina, E. Kage-Nakadai, S. Mitani, Murayama, S., Y. Ihara
  • Journal Title: PLoS One Volume: 9 Issue: 2 Pages: e89796-e89796
  • DOI: 10.1371/journal.pone.0089796
  • Peer Reviewed
• [Journal Article] Characterization of PUD-1 and PUD-2, Two Proteins Up-Regulated in a Long-Lived daf-2 Mutant (2013)
  • Author(s): Ding Y-H, Du Y-G, Luo S, Li Y-X, Li T-M, Yoshina S, Wang X, Klage K, Mitani S, Ye K, Dong M-Q
  • Journal Title: PLoS One Volume: 8 Issue: 6 Pages: e67158-e67158
  • DOI: 10.1371/journal.pone.0067158
  • Peer Reviewed
• [Presentation] Analysis of ADAMTS9/GON-1 function in insulin secretory cells and peripheral tissues (2016)
  • Author(s): Sawako Yoshina1, Shohei Mitani
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 北海道札幌市 札幌コンベンションセンター
  • Year and Date: 2016-03-22
• [Presentation] ADAMTS9 /GON-1 regulates insulin secretion and insulin signaling (2015)
  • Author(s): Sawako Yoshina, Shohei Mitani
  • Organizer: 第92回 日本生理学会大会
  • Place of Presentation: 神戸国際会議場・展示場
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] 小胞体におけるADAMTS9/GON-1の機能解析
  • Author(s): 吉名（茂泉） 佐和子
  • Organizer: 細胞生物学会
  • Place of Presentation: ウインクあいち