A conserved fertilization complex bridges sperm and egg in vertebrates

Area of Science:

• Reproductive biology
• Molecular mechanisms of fertilization
• Comparative genomics

Background:

• Fertilization involves sperm-egg binding and fusion, a process critical for sexual reproduction.
• While key proteins are known, the precise molecular interactions in vertebrate fertilization remain unclear.

Purpose of the Study:

• To identify novel proteins involved in sperm-egg interaction.
• To elucidate the molecular mechanisms of fertilization in vertebrates.

Main Methods:

• AlphaFold-Multimer screening to predict protein complex formation.
• Functional analysis of Tmem81 in zebrafish and mouse models.
• In vitro interaction studies of human orthologs.

Main Results:

• Identified Tmem81 as part of a conserved trimeric sperm complex with Izumo1 and Spaca6.
• Demonstrated Tmem81's essential role in male fertility in zebrafish and mice.
• Showed complex formation creates the binding site for the egg factor Bouncer in zebrafish.

Conclusions:

• A conserved sperm complex (Tmem81-Izumo1-Spaca6) mediates sperm-egg interaction across vertebrates.
• This complex binds divergent egg proteins (Bouncer in fish, JUNO in mammals).
• Presents a unified model for sperm-egg recognition in vertebrate reproduction.