FIGURE 4.

pH-dependent Ca²⁺ sensing by EFCAB9 to modulate CatSper channel activity A: Ca²⁺-dependent potentiation of the CatSper current (I_CatSper) in wild-type sperm under an intracellular alkaline condition. The traces are reproduced from Ref. 8, with permission from Cell. Inward I_CatSper is minimally affected by increasing Ca²⁺ concentration ([Ca²⁺]_i) under an acidic condition (pH_i 6.0; top), but greatly potentiated in a [Ca²⁺]_i-dependent manner under an alkaline condition (pH_i 7.4; bottom). B: a schematic cartoon of pH-dependent Ca²⁺-sensing of EFCAB9 in regulating CatSper channel activity. In acidic intracellular pH, EFCAB9 (EF9) and its binding partner, CATSPERζ (ζ), form a tight binary complex and respond marginally to increasing Ca²⁺ (top). After intracellular alkalinization, EFCAB9-CATSPERζ interactions weaken, which enhances Ca²⁺ sensitivity of EFCAB9 (bottom). Ca²⁺ binding to EF-hand domains changes EFCAB9 conformation to fully activate CatSper.