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Updated: Aug 27, 2025

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Medium-throughput Screening Assays for Assessment of Effects on Ca2+-Signaling and Acrosome Reaction in Human Sperm
Published on: March 1, 2019
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Human sperm TMEM95 binds eggs and facilitates membrane fusion
Shaogeng Tang1,2, Yonggang Lu3,4, Will M Skinner5
1Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305.
Summary
Transmembrane protein 95 (TMEM95) on sperm interacts with egg receptors, facilitating membrane fusion essential for fertilization. This interaction, mediated by a conserved charged region on TMEM95, is crucial for successful fertilization.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Cell Biology
Background:
- Transmembrane protein 95 (TMEM95) is a sperm acrosomal membrane protein.
- TMEM95 knockout in mice causes male-specific sterility, with sperm unable to fuse with eggs.
- The precise role of TMEM95 in sperm-egg membrane fusion remains unclear.
Purpose of the Study:
- To investigate the function of human TMEM95 in sperm-egg interactions.
- To identify the egg-binding domain and potential egg receptor for TMEM95.
- To elucidate the mechanism by which TMEM95 facilitates fertilization.
Main Methods:
- Sperm penetration assays using human sperm and hamster eggs.
- X-ray crystallography to determine the structure of TMEM95.
- Site-directed mutagenesis to alter specific amino acids in TMEM95.
- Monoclonal antibody production and functional assays.
Main Results:
- Human TMEM95 binds to hamster egg membranes, indicating an egg receptor.
- A conserved, positively charged region on TMEM95 is identified as the putative receptor-binding surface.
- Mutations in this region abolish TMEM95's egg-binding activity.
- Monoclonal antibodies against TMEM95 inhibit sperm-egg fusion but not sperm-egg binding.
Conclusions:
- Sperm TMEM95 engages in a specific, receptor-mediated interaction with eggs.
- This TMEM95-egg interaction is critical for facilitating membrane fusion during fertilization.
- TMEM95 represents a potential target for novel male contraceptive strategies.
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