Max Planck Institute for Neurobiology of Behavior-caesar, Molecular Sensory Systems, Ludwig-Erhard-Allee 2, 53175, Bonn, Germany.
Max Planck Institute for Multidisciplinary Sciences, Bioanalytical Mass Spectrometry, Am Fassberg 11, 37077, Göttingen, Germany.
Nat Commun. 2023 Sep 5;14(1):5395. doi: 10.1038/s41467-023-40855-0.
The reaction of CO with HO to form bicarbonate (HCO) and H controls sperm motility and fertilization via HCO-stimulated cAMP synthesis. A complex network of signaling proteins participates in this reaction. Here, we identify key players that regulate intracellular pH (pH) and HCO in human sperm by quantitative mass spectrometry (MS) and kinetic patch-clamp fluorometry. The resting pH is set by amiloride-sensitive Na/H exchange. The sperm-specific putative Na/H exchanger SLC9C1, unlike its sea urchin homologue, is not gated by voltage or cAMP. Transporters and channels implied in HCO transport are not detected, and may be present at copy numbers < 10 molecules/sperm cell. Instead, HCO is produced by diffusion of CO into cells and readjustment of the CO/HCO/H equilibrium. The proton channel H1 may serve as a unidirectional valve that blunts the acidification ensuing from HCO synthesis. This work provides a new framework for the study of male infertility.
CO 与 HO 反应生成碳酸氢盐（HCO）和 H，通过 HCO 刺激的 cAMP 合成来控制精子运动和受精。一个复杂的信号蛋白网络参与了这一反应。在这里，我们通过定量质谱（MS）和动力学膜片钳荧光法鉴定了调节人精子内 pH（pH）和 HCO 的关键因子。静息 pH 由阿米洛利敏感的 Na/H 交换设定。与海胆同源物不同，精子特异性假定 Na/H 交换体 SLC9C1 不受电压或 cAMP 的调控。未检测到涉及 HCO 转运的转运体和通道，它们的拷贝数< 10 个/精子细胞。相反，HCO 是通过 CO 扩散进入细胞和重新调整 CO/HCO/H 平衡产生的。质子通道 H1 可作为单向阀，阻止 HCO 合成引起的酸化。这项工作为男性不育的研究提供了一个新的框架。
