Studies on the extracellular transporting mechanisms of sperm proteasomes and the functions of PA200
| Project/Area Number |
17K19520
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biomedical structure and function and related fields
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Project Period (FY) |
2017-06-30 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | プロテアソーム / 精子 / 受精 / PA200 / ユビキチン / 細胞外 / 酵素 |
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| Outline of Final Research Achievements |
We previously reported that sperm proteasomes are involved in sperm penetration of the vitelline coat, probably as a lysin. Here, the localization of sperm proteasome in sperm membrane fraction was re-examined. Furthermore, roles in fertilization of proteasome activator PA200, which appears to be involved in sexual reproduction, was examined. The results showed that sperm proteasome subunits were detected by LC/MS in the immunoprecipitated sperm membrane fraction using anti-proteasome antibody. However, it was not successful to identify the proteasome-associating proteins. Then, targeting of ascidian PA200 genes was carried out by genome editing. However, this was not successful due to the induction of abnormal embryonic development. On the other hand, we noticed that sperm metalloproteases may be involved in ascidian fertilization based on the inhibitory effects on fertilization. This enzyme may also play a key role in fertilization together with the proteasome.
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| Academic Significance and Societal Importance of the Research Achievements |
申請者は、受精実験が容易な脊索動物マボヤを用いて、その受精に精子ユビキチン-プロテアソーム系が関与すること、特に細胞外で卵膜ライシンとして機能することを初めて明らかにした。その後、哺乳類や鳥類や棘皮動物でも同様の現象が確認され、新口動物に共通するシステムであると考えられる。一般に、プロテアソームは細胞内のタンパク質分解で重要な役割を果たすが、細胞外での機能は不明な点が多い。しかし、近年、神経疾患等で細胞外プロテアソームが注目されつつある。本研究は、受精に関わる精子プロテアソームの細胞外での機能と輸送機構に焦点を当てた研究であり、不妊症診断治療薬の開発に繋がりうる基礎研究といえる。
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Report
(4 results)
Research Products
(33 results)
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[Journal Article] Three multi-allelic gene pairs are responsible for self-sterility in the ascidian Ciona intestinalis2020
Author(s)
Sawada H, Yamamoto K, Yamaguchi A, Yamada L, Higuchi A, Nukaya H, Fukuoka M, Sakuma T, Yamamoto T, Sasakura Y, Shirae-Kurabayashi M
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Journal Title
Scientific Reports
Volume: 10
Issue: 1
Pages: 2514-2514
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Vitelline membrane proteins promote left-sided nodal expression after neurula rotation in the ascidian, Halocynthia roretzi.2019
Author(s)
Tanaka, Y., Yamada, S., Connop, S. L., Hashii, N., Sawada, H., Shih, Y., and Nishida, H.
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Journal Title
Dev. Biol.
Volume: 449
Issue: 1
Pages: 52-61
DOI
Related Report
Peer Reviewed
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[Journal Article] Chitin-based barrier immunity and Its loss predated mucus-colonization by indigenous gut microbiota.2018
Author(s)
Nakashima, K., Kimura, S., Ogawa, Y., Watanabe, S., Soma, S., Kaneko, T., Yamada, L., Sawada, H., Tung, C.-H., Lu, T-M., Yu, J-K., Briones, A. V., Kikuchi, S., and Satoh, N.
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Journal Title
Nature Communications
Volume: 9(1)
Issue: 1
Pages: 3402-3402
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The male gamete membrane protein DMP9/DAU2 is required for double fertilization in flowering plants.2018
Author(s)
Takahashi T., Mori, T., Ueda, K., Yamada, L., Nagahara, S., Higashiyama, T., Sawada, H., Igawa, T.
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Journal Title
Development
Volume: 145(23)
Issue: 23
DOI
Related Report
Peer Reviewed
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[Journal Article] Dual gene repertories for larval and adult shells reveal molecules for molluscan shell formation.2018
Author(s)
Zhao, R., Takeuchi, T., Luo, Y-J., Ishikawa, A., Kobayashi, T., Koyanagi, R., Villar-Briones, A., Yamada, L., Sawada, H., Iwanaga, S., Nagai, K., Satoh, N., and Endo, K.
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Journal Title
Molecular Biology and Evolution,
Volume: 35(11)
Pages: 2751-2761
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Haemorrhagic snake venom metalloproteases and human ADAMs cleave LRP5/6, which disrupts cell-cell adhesions in vitro and induces haemorrhage in vivo.2017
Author(s)
Seo T, Sakon T, Nakazawa S, Nishioka A, Watanabe K, Matsumoto K, Akasaka M, Shioi N, Sawada H, Araki S
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Journal Title
FEBS Journal
Volume: 284
Issue: 11
Pages: 1657-1671
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Vascular endothelial cell-cell adhesion disruption and hemorrhage are induced by truncated LRP5/6 which is processed by hemorrhagic snake venom metalloproteases2017
Author(s)
Seo, T., Kakon, T., Nakazawa, S., Nishioka, A., Watanabe, K., Matsumoto, K., Akasaka, M., Shioi, N., Sawada, H., and Araki, S.
Organizer
Gordon Research Conferences
Related Report
Int'l Joint Research
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[Book] Japanese Marine Life: A Practical Training Guide in Marine Biology (K. Inaba and J. Hall-Spencer, eds.) (執筆担当Gametes and fertilization, pp.93-107))2020
Author(s)
Inaba, k., Sawada, H., Yoshida, M., Shiba, K., Shirae-Kurabayashi, M. ほか
Total Pages
367
Publisher
Springer
ISBN
9789811513251
Related Report
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