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Updated: Sep 1, 2025
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Phosphopeptide Analysis of Rodent Epididymal Spermatozoa
Published on: December 30, 2014
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GRP78 plays a key role in sperm function via the PI3K/PDK1/AKT pathway
Woo-Jin Lee1, Eun-Ju Jung1, Ju-Mi Hwang1
1Department of Animal Science and Biotechnology, Kyungpook National University, Sangju, Gyeongsangbuk-do 37224, South Korea.
Reproductive Toxicology (Elmsford, N.Y.)
|August 16, 2022
Summary
Inhibiting Glucose-regulated protein 78 (GRP78) may harm sperm function. This study found GRP78 is crucial for sperm motility and capacitation, suggesting caution in cancer therapies targeting GRP78.
Area of Science:
- Reproductive Biology
- Molecular Cell Biology
- Cancer Research
Background:
- Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum protein vital for protein stability and the unfolded protein response.
- GRP78 is overexpressed on various cancer cells, making it a target for cancer therapies.
- The role of GRP78 in sperm physiology is largely unknown.
Purpose of the Study:
- To investigate the impact of GRP78 on sperm function during capacitation.
- To elucidate the molecular mechanisms by which GRP78 influences sperm physiology.
Main Methods:
- Boar spermatozoa were treated with HA15, a GRP78 antagonist.
- Evaluated sperm motility, kinematics, capacitation, viability, and tyrosine phosphorylation.
- Assessed levels of PI3K/PDK1/AKT pathway proteins.
Main Results:
- GRP78 inhibition by HA15 significantly reduced sperm motility, kinematics, capacitation, and viability.
- GRP78 expression decreased, and PI3K/PDK1/AKT pathway proteins and tyrosine phosphorylation were altered in HA15-treated sperm.
- These findings indicate GRP78 is important for sperm function.
Conclusions:
- GRP78 plays a significant role in regulating sperm function, including motility and capacitation.
- Inhibition of GRP78 may have adverse effects on sperm, potentially impacting fertility.
- Further research is needed to fully understand GRP78's molecular mechanisms in spermatozoa.
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