Extracellular domains of CATSPERε are essential for CatSper assembly during development and activity modulation in sperm capacitation.

The flagellar-specific Ca channel CatSper is a multiprotein complex that is critical for successful fertilization by controlling the sperm Ca signaling in space and time. Large extracellular domains (ECDs) of four single-pass transmembrane subunits, CATSPERβ, γ, δ, and ε, form a unique canopy structure over the pore-forming channel. However, the molecular mechanisms of canopy assembly during development and its physiological function in mature sperm remain unknown.