Sperm protein crucial for gamete fusion discovered

The discovery of a protein responsible for binding and fusing sperm and egg cells in mice could shed light on possible causes of infertility and treatments for it.

During fertilisation, there is a two-step process by which the sperm and egg must first bind to each other and then fuse together, the act of the sharing of genetic and other information. New research, published in the Journal of Cell Biology, has discovered that the protein IZUMO1, previously identified as involved in the binding of the sperm to the egg in mammals also has a role in the fusing process.

There is some evidence that some men with infertility have low expression of IZUMO1, but the discovery also has implications for contraceptive research. 'One possibility is to find ways to inhibit IZUMO1's fusogenic ability,' Dr Nicholas Brukman, first author of the paper said. 'We can try to design drugs to block one function, the other or both [binding & fusing].'

Previously, researchers have shown that the membranes of the egg and sperm cells bind together due to the interaction of the JUNO protein (see BioNews 1159) on the surface of the egg cell and the IZUMO1 protein on the surface of the sperm cell. However, IZUMO1 was identified as a key in that it is crucial for the fusion of the sperm and egg into a single cell, the zygote which develops to become an embryo. IZUMO1 is the first fusogenic (ie, involved in the fusing of cells) protein in mammalian sex cells to be discovered. While the experiments were done in mice, the same genes are present in sperm and eggs in humans.

Experiments showed the binding and fusing domains of IZUMO1 appear to be separate, as the binding and fusing mechanisms are able to work independently. IZUMO1 can induce fusion even when there is a mutation that prevents binding, and another mutation can induce binding with JUNO without inducing fusion. IZUMO1 was already known to be related to male fertility, as in mice with impaired IZUMO1 protein expression were infertile, although this was not due to lack of sperm, but instead sperm that did not function properly.

Some infertile men have lower IZUMO1 levels, which could now be understood as a potential mechanism that causes infertility. Additionally, some women have been identified as having IZUMO1 antibodies, which could lead to either failed binding or failed fusion, both of which are potential causes of infertility.