Chloride Intracellular Channel 4 (CLIC4) controls volume regulation in sperm development via Protein Kinase C (PKC)
Veronica Loyo-Celis1, Shridhar Sanghvi1,2, Satish K Raut1
1Department of Physiology and Cell Biology, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, United States.
BMC Biology
|February 20, 2026
Summary
Chloride Intracellular Channel 4 (CLIC4) regulates sperm cell volume during maturation by modulating chloride fluxes. This discovery offers new insights into sperm osmoregulation and potential treatments for male infertility.
Area of Science:
- Sperm physiology and male reproductive health.
Background:
- Chloride ions (Cl) are crucial for sperm function, including motility and fertilization.
- Disruptions in Cl homeostasis lead to impaired sperm function and male infertility.
- The molecular mechanisms of sperm volume regulation remain incompletely understood.
Purpose of the Study:
- To investigate the role of Chloride Intracellular Channel 4 (CLIC4) in sperm physiology.
- To elucidate the molecular components governing sperm volume regulation.
Main Methods:
- Utilized patch-clamp electrophysiology and biochemical analyses (western blotting, immunocytochemistry).
- Examined sperm cells from wild-type and CLIC4-null mutant mice.
- Assessed sperm motility, morphology, and acrosome reaction.
Main Results:
- Identified novel IAA-94-sensitive chloride currents in mouse sperm.
- Demonstrated that CLIC4 mediates these currents and regulates sperm volume during maturation.
- Found that CLIC4's activity is modulated by Protein Kinase C (PKC).
Conclusions:
- CLIC4 is essential for sperm cell volume regulation and chloride flux modulation during maturation.
- These findings enhance understanding of sperm osmoregulation.
- The study may inform novel therapeutic strategies for male infertility.
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