LRRC52 is likely a functional component of human KSper†
Jiali Zhang1, Liping Zheng2, Ying Chen2
1Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, Jiangsu, China.
Biology of Reproduction
|January 24, 2024
Summary
Leucine-rich-repeat-containing protein 52 (LRRC52) is crucial for sperm potassium channel (KSper) function in both mice and humans. This study developed an antibody, LID1, to show LRRC52 regulates KSper, impacting sperm motility and fertilization.
Area of Science:
- Reproductive Biology
- Ion Channel Physiology
- Sperm Function
Background:
- Sperm capacitation involves membrane potential hyperpolarization, primarily regulated by sperm potassium channels (KSper).
- The KSper channel requires both a pore-forming subunit (SLO3) and an auxiliary subunit (LRRC52) for function.
- The role of human LRRC52 (hLRRC52) in human KSper (hKSper) and sperm function remains unclear.
Purpose of the Study:
- To investigate the role of LRRC52 in KSper function in both mice and humans.
- To determine if hLRRC52 is essential for hKSper conductance and human sperm physiology.
- To elucidate the regulatory mechanism of LRRC52 on KSper.
Main Methods:
- Development of a polyclonal antibody (LID1) targeting a conserved extracellular segment of LRRC52.
- Co-immunoprecipitation to assess LRRC52 and SLO3 interaction.
- Patch-clamp electrophysiology to record KSper currents in mouse and human sperm.
- Assessment of sperm functions including motility and acrosome reaction.
Main Results:
- LID1 specifically detected LRRC52 and co-immunoprecipitated with SLO3 in mice.
- LID1 treatment significantly attenuated mouse KSper (mKSper) activation and sperm function.
- Human LRRC52 (hLRRC52) is expressed in human sperm and associates with hSLO3.
- LID1 inhibited hKSper currents, depolarized human sperm membrane potential, and impaired Ca2+ signaling, motility, and acrosome reaction.
- LID1 selectively inhibited KSper channels without affecting CatSper channels.
Conclusions:
- LRRC52 is an essential auxiliary subunit for both mouse and human KSper channel function.
- hLRRC52 plays a critical role in regulating hKSper activity and modulating human sperm physiological functions.
- Targeting LRRC52 offers a potential strategy for modulating sperm function.
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