Related Experiment Video
Updated: Nov 4, 2025
Phosphopeptide Analysis of Rodent Epididymal Spermatozoa
Published on: December 30, 2014
Dissecting the PRSS37 interactome and potential mechanisms leading to ADAM3 loss in PRSS37-null sperm
Wenfeng Xiong1, Chunling Shen1, Chaojie Li1
1State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200025, China.
Abstract:
A disintegrin and metalloproteinase 3 (ADAM3) is a sperm membrane protein critical for sperm migration from the uterus into the oviduct and sperm-egg binding in mice. Disruption of PRSS37 results in male infertility concurrent with the absence of mature ADAM3 from cauda epididymal sperm. However, how PRSS37 modulates ADAM3 maturation remains largely unclear. Here, we determine the PRSS37 interactome by GFP immunoprecipitation coupled with mass spectrometry in PRSS37-EGFP knock-in mice. Three molecular chaperones (CLGN, CALR3 and PDILT) and three ADAM proteins (ADAM2, ADAM6B and ADAM4) were identified to be interacting with PRSS37. Coincidently, five of them (except ADAM4) have been reported to interact with ADAM3 precursor and regulate its maturation. We further demonstrated that PRSS37 also interacts directly with ADAM3 precursor and its deficiency impedes the association between PDILT and ADAM3. This could contribute to improper translocation of ADAM3 to the germ cell surface, leading to ADAM3 loss in PRSS37-null mature sperm. The understanding of the maturation mechanisms of pivotal sperm plasma membrane proteins will pave the way toward novel strategies for contraception and the treatment of unexplained male infertility.
Insights
The protein PRSS37 is essential for male fertility by regulating the maturation of ADAM3, a sperm protein crucial for fertilization. Its absence leads to infertility due to improper ADAM3 processing and sperm function.
Area of Science:
- Reproductive Biology
- Molecular Cell Biology
- Biochemistry
Background:
- ADAM3 (a disintegrin and metalloproteinase 3) is vital for sperm function, including migration and egg binding.
- PRSS37 deficiency causes male infertility and absence of mature ADAM3 in sperm.
- The precise mechanism by which PRSS37 influences ADAM3 maturation is not well understood.
Purpose of the Study:
- To elucidate the molecular interactions of PRSS37.
- To understand how PRSS37 regulates the maturation of ADAM3.
- To identify potential therapeutic targets for male infertility.
Main Methods:
- GFP immunoprecipitation coupled with mass spectrometry in PRSS37-EGFP knock-in mice.
- Analysis of protein-protein interactions.
- Investigating the effect of PRSS37 deficiency on ADAM3 maturation and localization.
Main Results:
- PRSS37 interacts with molecular chaperones (CLGN, CALR3, PDILT) and ADAM proteins (ADAM2, ADAM6B, ADAM4).
- PRSS37 directly interacts with the ADAM3 precursor.
- PRSS37 deficiency disrupts the PDILT-ADAM3 association, impairing ADAM3 translocation to the germ cell surface.
Conclusions:
- PRSS37 plays a critical role in ADAM3 maturation and proper sperm surface localization.
- Dysregulation of the PRSS37-ADAM3 interaction pathway contributes to male infertility.
- Understanding these mechanisms may lead to new strategies for contraception and treating male infertility.
