A conserved fertilization complex bridges sperm and egg in vertebrates
Fertilization, the basis for sexual reproduction, culminates in the binding and fusion of sperm and egg. Although several proteins are known to be crucial for this process in vertebrates, the molecular mechanisms remain poorly understood. Using an AlphaFold-Multimer screen, we identified the protein Tmem81 as part of a conserved trimeric sperm complex with the essential fertilization factors Izumo1 and Spaca6. We demonstrate that Tmem81 is essential for male fertility in zebrafish and mice. In line with trimer formation, we show that Izumo1, Spaca6, and Tmem81 interact in zebrafish sperm and that the human orthologs interact in vitro. Notably, complex formation creates the binding site for the egg fertilization factor Bouncer in zebrafish. Together, our work presents a comprehensive model for fertilization across vertebrates, where a conserved sperm complex binds to divergent egg proteins-Bouncer in fish and JUNO in mammals-to mediate sperm-egg interaction.
Authors
- Xinyin Wang (ORCID: https://orcid.org/0009-0004-9053-458X)
- Theresa Humer
- Joachim M. Surm (ORCID: https://orcid.org/0000-0001-6970-029X)
- Karel Stejskal (ORCID: https://orcid.org/0000-0001-7835-8123)
- Dominik Handler (ORCID: https://orcid.org/0000-0002-1059-4960)
- Victoria E. Deneke (ORCID: https://orcid.org/0000-0002-4404-8706)
- Gabriela Krššáková
- Yehu Moran (ORCID: https://orcid.org/0000-0001-9928-9294)
- Andrea Pauli (ORCID: https://orcid.org/0000-0001-9646-2303)
- Yonggang Lu (ORCID: https://orcid.org/0000-0003-0198-8906)
- Elisabeth Roitinger (ORCID: https://orcid.org/0000-0002-3405-7801)
- Maki Kamoshita (ORCID: https://orcid.org/0009-0009-7853-5164)
- Masahito Ikawa (ORCID: https://orcid.org/0000-0001-9859-6217)
- Andreas Blaha (ORCID: https://orcid.org/0000-0002-0995-4228)
- Alexander Schleiffer (ORCID: https://orcid.org/0000-0001-6251-2747)
- Jonne M. Draper (ORCID: https://orcid.org/0009-0004-7664-212X)
- Karin Panser (ORCID: https://orcid.org/0000-0002-0170-1867)
- Tyler D. R. Vance (ORCID: https://orcid.org/0000-0002-7637-5891)
- Clara S. Phan
- Jeffrey E. Lee (ORCID: https://orcid.org/0000-0002-2172-6586)
- Laurine Jacob
- Johannes P Suwita
Institutions
- Institute of Molecular Biotechnology (AT)
- Austrian Academy of Sciences (AT)
- University of Toronto (CA)
- Research Institute of Molecular Pathology (AT)
- Hebrew University of Jerusalem (IL)
- Vienna Biocenter (AT)
- The University of Osaka (JP)
Publication Details
- Journal
- Cell
- Published
- 2024-10-17
- DOI
- https://doi.org/10.1016/j.cell.2024.09.035
- Citations
- 53
- Primary Topic
- Reproductive Biology and Fertility
- Type
- article
- Field-Weighted Citation Impact
- 28.78
Funders
- Human Frontier Science Program
- Government of Ontario
- United States-Israel Binational Science Foundation
- Austrian Science Fund
- Israel Science Foundation
- Österreichische Forschungsförderungsgesellschaft
- Boehringer Ingelheim Stiftung
- Canadian Institutes of Health Research
- Japan Society for the Promotion of Science
- Japan Science and Technology Agency
- H2020 European Research Council