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Updated: Jul 15, 2026
Analysis of Epididymal Protein Synthesis and Secretion
Published on: August 25, 2018
Identification of an ADAM2-ADAM3 complex on the surface of mouse testicular germ cells and cauda epididymal sperm
Hitoshi Nishimura1, Diana G Myles, Paul Primakoff
1Department of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis, California 95618, USA.
Abstract:
Male mice lacking ADAM2 (fertilin beta) or ADAM3 (cyritestin) are infertile; cauda epididymal sperm (mature sperm) from these mutant mice cannot bind to the egg zona pellucida. ADAM3 is barely present in Adam2-null sperm, despite normal levels of this protein in Adam2-null testicular germ cells (TGCs; sperm precursor cells). Here, we have explored the molecular basis for the loss of ADAM3 in Adam2-null TGCs to clarify the biosynthetic and functional linkage of ADAM2 and ADAM3. A small portion of total ADAM3 was found present on the surface of wild-type and Adam2(-/-) TGCs at similar levels. In the Adam2-null TGCs, however, surface-localized ADAM3 exhibited an increased amount of an endoglycosidase H-resistant form that may be related to instability of ADAM3. Moreover, we found a complex between ADAM2 and ADAM3 on the surface of TGCs and sperm. The intracellular chaperone calnexin was a component of the testicular ADAM2-ADAM3 complex. Our findings suggest that the association with ADAM2 is a key element for stability of ADAM3 in epididymal sperm. The presence of the ADAM2-ADAM3 complex in sperm also suggests a potential role of ADAM2 with ADAM3 in sperm binding to the egg zona pellucida.
Insights
Male mice lacking ADAM2 or ADAM3 are infertile due to sperm dysfunction. ADAM2 protein is crucial for ADAM3 stability in sperm, enabling egg binding.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Cell Biology
Background:
- Male infertility can result from defects in sperm-egg binding.
- ADAM2 (fertilin beta) and ADAM3 (cyritestin) are essential for sperm to bind the egg zona pellucida.
- ADAM3 is significantly reduced in sperm lacking ADAM2, despite normal levels in precursor cells.
Purpose of the Study:
- To investigate the molecular mechanisms behind ADAM3 loss in ADAM2-deficient sperm.
- To elucidate the relationship between ADAM2 and ADAM3 biosynthesis and function.
- To clarify the role of ADAM2 in ADAM3 stability and sperm function.
Main Methods:
- Analysis of ADAM3 localization and forms in wild-type and Adam2(-/-) testicular germ cells (TGCs) and sperm.
- Investigation of protein complexes involving ADAM2 and ADAM3 using co-immunoprecipitation.
- Assessment of the role of intracellular chaperones, such as calnexin, in the ADAM2-ADAM3 complex.
Main Results:
- Surface levels of ADAM3 were similar in wild-type and Adam2(-/-) TGCs.
- ADAM2-null TGCs showed increased endoglycosidase H-resistant ADAM3, suggesting instability.
- ADAM2 and ADAM3 form a complex on the surface of TGCs and sperm, with calnexin associated with the testicular complex.
Conclusions:
- ADAM2 association is critical for maintaining ADAM3 stability in epididymal sperm.
- The ADAM2-ADAM3 complex in sperm suggests a collaborative role in sperm-zona pellucida binding.
- Understanding this interaction is key to addressing male infertility related to sperm-egg interaction defects.
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