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CatSper's histidine-rich end offers a model of temperature sensitivity

A single peer-reviewed study proposes that histidine-rich regions help neighbouring CatSper channels open together as temperature and acidity change. Comparisons across 47 species and structural modelling were paired with mouse sperm measurements showing reduced temperature responses after prolonged capacitation. The proposed molecular contacts remain predictions requiring direct validation; the results concern channel regulation and provide no tested treatment for human infertility.

Science··Morning
A fine electrode and probe reach a clear fluid chamber on a metal microscope stage, with transparent tubing attached.

Histidine-rich regions may connect neighbouring channels

A single peer-reviewed study proposes a molecular connection between temperature, acidity and CatSper, the channel that controls calcium entry into sperm. Histidine, an amino acid, appears in clusters near the beginning of its CatSper1 subunit. The proposed contacts between adjacent channel complexes depend on histidine's charge. Changes in temperature and pH may therefore help coordinate channel opening.[1]

Ordered channel rows extend through the sperm tail. The calcium they admit supports the vigorous tail movement required for fertilization. Temperature, intracellular acidity and membrane voltage all regulate activity, making coordinated opening a question about the channel's organization as well as its individual parts.[1]

Species comparisons link histidine to fertilization temperature

Researchers compared sequences across 47 species and built structural models using AlphaFold3, a protein-structure modelling system, alongside earlier electron-microscopy data. CatSper1's N-terminal length and histidine content correlated with fertilization temperature. Two subterranean mole rat species departed from the general pattern. A possible explanation involving their carbon-dioxide-rich environment remains uncertain because measurements of acidity in those animals’ reproductive tracts are lacking.[1]

Mouse sperm loses part of its temperature response

Electrical measurements and calcium imaging found weaker temperature-dependent CatSper activity after prolonged capacitation, the maturation process that prepares sperm for fertilization. Sperm lacking CatSper1 supplied controls. Earlier studies linked these conditions to partial cleavage of its starting region. The molecular contacts proposed here still need direct structural validation. These mouse experiments measured channel function, without testing a human infertility treatment.[1]

References

  1. News sourcePLOS BiologyA histidine-based model links sperm channel activation to temperature↩1↩2↩3↩4