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Updated: Jun 25, 2026

Medium-throughput Screening Assays for Assessment of Effects on Ca2+-Signaling and Acrosome Reaction in Human Sperm
Published on: March 1, 2019
Mammalian fertilization: the strange case of sperm protein 56
1Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029-6574, USA. paul.wassarman@mssm.edu
Abstract:
During mammalian fertilization sperm bind to the egg's zona pellucida (ZP) after undergoing capacitation. Capacitated mouse sperm bind to mZP3 (one of three ZP glycoproteins), undergo the acrosome reaction, penetrate the ZP, and fuse with egg plasma membrane. Sperm protein 56 (sp56), a member of the C3/C4 superfamily of binding proteins, was identified nearly 20 years ago as a binding partner for mZP3 by photoaffinity cross-linking of acrosome-intact sperm. However, subsequent research revealed that sp56 is a component of the sperm's acrosomal matrix and, for sperm with an intact acrosome, should be unavailable for binding to mZP3. Recently, this dilemma was resolved when it was recognized that some acrosomal matrix (AM) proteins, including sp56, are released to the sperm surface during capacitation. This may explain why uncapacitated mammalian sperm are unable to bind to the unfertilized egg ZP.
Insights
Sperm protein 56 (sp56) is released to the sperm surface during capacitation, enabling binding to the egg zona pellucida (ZP). This explains why uncapacitated sperm cannot bind to the ZP.
Area of Science:
- Reproductive biology
- Cellular and molecular biology
- Biochemistry
Background:
- Mammalian fertilization involves sperm binding to the egg's zona pellucida (ZP) after capacitation.
- Sperm protein 56 (sp56) was previously identified as a zona pellucida glycoprotein mZP3 binding partner.
- sp56 is located in the sperm's acrosomal matrix, posing a question about its binding availability.
Purpose of the Study:
- To resolve the apparent paradox of sp56 binding to mZP3.
- To investigate the role of sp56 release during sperm capacitation.
Main Methods:
- Photoaffinity cross-linking of acrosome-intact sperm.
- Analysis of acrosomal matrix (AM) protein localization during capacitation.
Main Results:
- sp56 is a component of the sperm acrosomal matrix.
- sp56 is released to the sperm surface during capacitation.
- This release mechanism potentially explains sperm-zona pellucida binding.
Conclusions:
- Capacitation-induced release of sp56 to the sperm surface facilitates binding to the zona pellucida.
- This finding clarifies the mechanism of sperm-egg interaction during fertilization.
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