PUBLICATION
A conserved fertilization complex bridges sperm and egg in vertebrates
- Authors
- Deneke, V.E., Blaha, A., Lu, Y., Suwita, J.P., Draper, J.M., Phan, C.S., Panser, K., Schleiffer, A., Jacob, L., Humer, T., Stejskal, K., Krssakova, G., Roitinger, E., Handler, D., Kamoshita, M., Vance, T.D.R., Wang, X., Surm, J.M., Moran, Y., Lee, J.E., Ikawa, M., Pauli, A.
- ID
- ZDB-PUB-241020-3
- Date
- 2024
- Source
- Cell 187(25): 7066-7078.e22 (Journal)
- Registered Authors
- Blaha, Andreas, Deneke, Victoria, Panser, Karin, Pauli, Andrea
- Keywords
- AlphaFold, gamete adhesion, male fertility, protein-protein interaction, sperm proteome, sperm-egg interaction, vertebrate fertilization, zebrafish
- MeSH Terms
-
- Animals
- Female
- Fertilization*
- Humans
- Immunoglobulins/metabolism
- Male
- Membrane Proteins*/metabolism
- Mice
- Ovum/metabolism
- Sperm-Ovum Interactions*
- Spermatozoa*/metabolism
- Zebrafish*/metabolism
- Zebrafish Proteins*/metabolism
- PubMed
- 39423812 Full text @ Cell
Citation
Deneke, V.E., Blaha, A., Lu, Y., Suwita, J.P., Draper, J.M., Phan, C.S., Panser, K., Schleiffer, A., Jacob, L., Humer, T., Stejskal, K., Krssakova, G., Roitinger, E., Handler, D., Kamoshita, M., Vance, T.D.R., Wang, X., Surm, J.M., Moran, Y., Lee, J.E., Ikawa, M., Pauli, A. (2024) A conserved fertilization complex bridges sperm and egg in vertebrates. Cell. 187(25):7066-7078.e22.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping