CFTR modulates aquaporin-mediated glycerol permeability in mouse Sertoli cells

by Selleckchem | May 24 2023

The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel that is crucial for fluid homeodynamics throughout the male reproductive tract. Previous evidence shed light on a potential molecular partnership between this channel and aquaporins (AQPs). Herein, we explore the role of CFTR on AQPs-mediated glycerol permeability in mouse Sertoli cells (mSCs). We were able to identify the expression of CFTR, AQP3, AQP7, and AQP9 in mSCs by RT-PCR, Western blot, and immunofluorescence techniques. Cells were then treated with CFTRinh-172, a specific CFTR inhibitor, and its glycerol permeability was evaluated by stopped-flow light scattering. We observed that CFTR inhibition decreased glycerol permeability in mSCs by 30.6% when compared to the control group. A DUOLINK proximity ligation assay was used to evaluate the endogenous protein-protein interactions between CFTR and the various aquaglyceroporins we identified. We positively detected that CFTR is in close proximity with AQP3, AQP7, and AQP9 and that, through a possible physical interaction, CFTR can modulate AQP-mediated glycerol permeability in mSCs. As glycerol is essential for the control of the blood-testis barrier and elevated concentration in testis results in the disruption of spermatogenesis, we suggest that the malfunction of CFTR and the consequent alteration in glycerol permeability is a potential link between male infertility and cystic fibrosis.

Comments：

The study you described explored the potential molecular partnership between the cystic fibrosis transmembrane conductance regulator (CFTR) and aquaporins (AQPs) in mouse Sertoli cells (mSCs). CFTR is an anion channel that plays a crucial role in fluid homeodynamics throughout the male reproductive tract, and AQPs are membrane proteins that facilitate the transport of water and small solutes such as glycerol.

The study used RT-PCR, Western blot, and immunofluorescence techniques to identify the expression of CFTR, AQP3, AQP7, and AQP9 in mSCs. The researchers then treated the cells with CFTRinh-172, a specific CFTR inhibitor, and evaluated its effect on glycerol permeability using stopped-flow light scattering. They observed that CFTR inhibition decreased glycerol permeability in mSCs by 30.6% compared to the control group.

To investigate the protein-protein interactions between CFTR and the various aquaglyceroporins they identified, the researchers used a DUOLINK proximity ligation assay. They positively detected that CFTR is in close proximity with AQP3, AQP7, and AQP9, suggesting that CFTR can modulate AQP-mediated glycerol permeability in mSCs through a possible physical interaction.

The study suggests that the malfunction of CFTR and the consequent alteration in glycerol permeability could be a potential link between male infertility and cystic fibrosis. Glycerol is essential for the control of the blood-testis barrier, and elevated concentrations in the testis can result in the disruption of spermatogenesis. Therefore, the findings of this study provide important insights into the molecular mechanisms underlying male infertility and cystic fibrosis.