Related Experiment Video

Updated: Aug 27, 2025

Medium-throughput Screening Assays for Assessment of Effects on Ca2+-Signaling and Acrosome Reaction in Human Sperm
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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.

Proceedings of the National Academy of Sciences of the United States of America
|September 26, 2022
PubMed

Insights

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.
Keywords:
TMEM95fertilizationmembrane fusionsperm–egg fusion

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