Regulation of IZUMO1-JUNO in mammalian gamete fusion

• Project/Area Number: 17K15128
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Developmental biology
• Research Institution: Shizuoka University (2021); Fukushima Medical University (2017-2020)
• Principal Investigator: Saito Takako 静岡大学, 農学部, 助教 (10778038)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 受精 / 精子 / 卵子 / 膜融合 / IZUMO1 / JUNO / 遺伝子改変マウス / 発生

Outline of Final Research Achievements

Sperm-egg fusion is accomplished through interaction of a specific set of membrane proteins in each gamete: sperm IZUMO1 and oocyte JUNO. In this study, we produced mouse lines having different levels of IZUMO1 expression and point mutations in IZUMO1 for JUNO binding site by the CRISPR/Cas9 system. We observed that the mouse fertilization rate is highly affected by the density of IZUMO1 protein in sperm using gene modified mouse lines. These results suggest that evaluating IZUMO1 protein levels is useful for predicting fecundity, and suitable as a test for male fertility. Also we revealed that IZUMO1-JUNO interaction is essential for the beginning of gamete fusion.

Academic Significance and Societal Importance of the Research Achievements

受精における膜融合は、同種異個体の細胞同士が融合するという他では例のない現象である。有性生殖の最大の利点である遺伝子の多様性を造り出すためにも、精子と卵子の融合は生物にとって最も重要な機構の一つである。IZUMO1-JUNOによって厳密に制御されている配偶子膜融合の解明を足がかりに、個体発生分化で起こる細胞間認識と融合の機構についても理解が広まると期待できる。

Research Products

• [Journal Article] Fertilization of Ascidians: Gamete Interaction, Self/Nonself Recognition and Sperm Penetration of Egg Coat (2022)
  • Author(s): Saito Takako、Sawada Hitoshi
  • Journal Title: Frontiers in Cell and Developmental Biology Volume: 9 Pages: 827214-827214
  • DOI: 10.3389/fcell.2021.827214
  • Peer Reviewed / Open Access
• [Journal Article] Removal of the block to self-fertilization by low-calcium artificial seawater in the ascidian Ciona intestinalis. (2022)
  • Author(s): Shizuya Hashimoto, Keita Kinjo, Takako Saito, Hitoshi Sawada,
  • Journal Title: Zygote Volume: -
  • Peer Reviewed
• [Journal Article] Emerging Role of TCA Cycle-Related Enzymes in Human Diseases (2021)
  • Author(s): Kang Woojin、Suzuki Miki、Saito Takako、Miyado Kenji
  • Journal Title: International Journal of Molecular Sciences Volume: 22 Issue: 23 Pages: 13057-13057
  • DOI: 10.3390/ijms222313057
  • Peer Reviewed / Open Access
• [Journal Article] Sperm IZUMO1-Dependent Gamete Fusion Influences Male Fertility in Mice (2019)
  • Author(s): Saito Takako、Wada Ikuo、Inoue Naokazu
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 19 Pages: 4809-4809
  • DOI: 10.3390/ijms20194809
  • Peer Reviewed / Open Access
• [Journal Article] Alternative splicing of the Izumo1 gene ensures triggering gamete fusion in mice. (2019)
  • Author(s): Takako Saito, Ikuo Wada, and Naokazu Inoue
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 3151-3151
  • DOI: 10.1038/s41598-019-40130-7
  • Peer Reviewed / Open Access
• [Presentation] Sperm IZUMO1 dependent gamete fusion influences male fertility in mice (2019)
  • Author(s): Saito Takako、Wada Ikuo、Inoue Naokazu
  • Organizer: Gordon Research Conferences
  • Int'l Joint Research
• [Presentation] Izumo1遺伝子の選択的スプライシングによってマウスの配偶子融合は保証される (2019)
  • Author(s): 齋藤貴子、和田郁夫、井上直和
  • Organizer: 第90回日本動物学会
• [Presentation] Alternative splicing of the Izumo1 gene ensures triggering gamete fusion in mice (2019)
  • Author(s): 齋藤貴子、和田郁夫、井上直和
  • Organizer: 第42回日本分子生物学会