The life of every sexually reproducing organism begins with the process of fertilization. In order for fertilization to take place, a sperm must find, recognize and fuse with an egg. Despite the fundamental nature of this process, it is not understood how these two cells interact on a molecular level. A recent study, led by the HFSP Awardees Victoria Deneke and Andrea Pauli, discovers the molecular machinery that bridges sperm and egg.
The scientists utilized AlphaFold, which was awarded the 2024 Nobel Prize in Chemistry, to uncover a tripartite protein complex that forms on the sperm and is composed of two previously known proteins, Izumo1 and Spaca6, and an uncharacterized protein, Tmem81. The team showed that the proteins in this complex interact in zebrafish sperm and that their human counterparts could interact in vitro.
Furthermore, the group of researchers found that this fertilization complex provides the first molecular link between sperm and egg, bringing their plasma membranes in close proximity before they fuse. In fish, the sperm complex interacts with Bouncer, while in mammals it interacts with the evolutionarily and structurally unrelated protein JUNO. This suggests that the machinery on the sperm has remained the same throughout many years of evolution, while the receptors on the egg have diverged between mammals and non-mammals.
The current work was supported by an HFSP Long Term Fellowship to Victoria Deneke as well as an HFSP Young Investigator Grant to Andrea Pauli. Future studies will delve into how this machinery, together with other proteins, mediate the fusion between sperm and egg to complete the fertilization process.