The sodium-proton exchangers sNHE and NHE1 control plasma membrane hyperpolarization in mouse sperm.

IF 4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Biological Chemistry Pub Date : 2024-10-28 DOI:10.1016/j.jbc.2024.107932

Analia G Novero, Paulina Torres Rodríguez, José L De la Vega Beltrán, Liza J Schiavi-Ehrenhaus, Guillermina M Luque, Micaela Carruba, Cintia Stival, Iñaki Gentile, Carla Ritagliati, Celia M Santi, Takuya Nishigaki, Diego Krapf, Mariano G Buffone, Alberto Darszon, Claudia L Treviño, Dario Krapf

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引用次数: 0

Abstract

Sperm capacitation is a complex process that takes place in the female reproductive tract and empowers mammalian sperm with the competence to fertilize an egg. It consists of an intricate cascade of events that can be mimicked in vitro through incubation in a medium containing essential components such as bicarbonate, albumin, Ca²⁺ and energy substrates, among others. Genetic and pharmacological studies have underscored the unique significance of the K⁺ channel SLO3 in membrane potential hyperpolarization, as evidenced by the infertility of mice lacking its expression. Notably, two key molecular events, sperm hyperpolarization and intracellular alkalinization, are central to the capacitation process. SLO₃ is activated by alkalinization. However, the molecular mechanisms responsible for intracellular alkalization and activation of SLO₃ are not completely understood. In this study, we examined the impact of Na⁺/H⁺ exchangers on mouse sperm membrane hyperpolarization during capacitation. Pharmacological inhibition of the NHE₁ exchanger blocked membrane hyperpolarization. A similar effect was observed in sperm deficient of the Ca²⁺ channel CatSper, because of NHE₁ not being activated by Ca²⁺. In addition, the sperm specific NHE (sNHE) KO, did not show membrane hyperpolarization upon capacitation or induction with cAMP analogues. Our results show that sNHE is dually modulated by cAMP and membrane hyperpolarization probably through its cyclic nucleotide binding domain and the voltage-sensor motif respectively. Together, sNHE and NHE1provide the alkalinization need for SLO₃ activation during capacitation.

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钠-质子交换器 sNHE 和 NHE1 控制着小鼠精子质膜的超极化。

精子获能是在女性生殖道中发生的一个复杂过程，它赋予哺乳动物精子受精卵的能力。它由一系列错综复杂的事件组成，可通过在含有碳酸氢盐、白蛋白、Ca2+ 和能量底物等重要成分的培养基中进行体外模拟。遗传学和药理学研究强调了 K+ 通道 SLO3 在膜电位超极化中的独特意义，缺乏其表达的小鼠不育就是证明。值得注意的是，精子超极化和细胞内碱化这两个关键分子事件是获能过程的核心。SLO3 通过碱化被激活。然而，细胞内碱化和 SLO3 激活的分子机制尚未完全明了。在这项研究中，我们研究了 Na+/H+ 交换器对获能过程中小鼠精子膜超极化的影响。对 NHE1 交换子的药理抑制阻止了膜超极化。在缺乏 Ca2+ 通道 CatSper 的精子中也观察到了类似的效果，因为 NHE1 不会被 Ca2+ 激活。此外，精子特异性 NHE（sNHE）KO 在获能或用 cAMP 类似物诱导时没有显示膜超极化。我们的研究结果表明，sNHE 可能分别通过其环核苷酸结合结构域和电压传感器基序，受到 cAMP 和膜超极化的双重调控。在获能过程中，sNHE 和 NHE1 共同提供了 SLO3 激活所需的碱化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Biological Chemistry Biochemistry, Genetics and Molecular Biology-Biochemistry

自引率

4.20%

发文量

1233

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