Laboratory of Cell Signal Transduction Networks, Instituto de Biología Molecular y Celular de Rosario (IBR), CONICET-UNR, Rosario, Argentina; Laboratorio de Medicina Reproductiva (LMR), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.
Laboratory of Cell Signal Transduction Networks, Instituto de Biología Molecular y Celular de Rosario (IBR), CONICET-UNR, Rosario, Argentina.
Mol Cell Endocrinol. 2020 Dec 1;518:110992. doi: 10.1016/j.mce.2020.110992. Epub 2020 Aug 24.
The 3', 5'-cyclic adenosine monophosphate (cAMP) dependent protein kinase (PKA) is a tetrameric holoenzyme comprising a set of two regulatory subunits (PKA-R) and two catalytic (PKA-C) subunits. The PKA-R subunits act as sensors of cAMP and allow PKA-C activity. One of the first signaling events observed during mammalian sperm capacitation is PKA activation. Thus, understanding how PKA activity is restricted in space and time is crucial to decipher the critical steps of sperm capacitation. It is widely accepted that PKA specificity depends on several levels of regulation. Anchoring proteins play a pivotal role in achieving proper localization signaling, subcellular targeting and cAMP microdomains. These multi-factorial regulation steps are necessary for a precise spatio-temporal activation of PKA. Here we discuss recent understanding of regulatory mechanisms of PKA in mammalian sperm, such as post-translational modifications, in the context of its role as the master orchestrator of molecular events conducive to capacitation.
3'，5'-环腺苷酸（cAMP）依赖性蛋白激酶（PKA）是一种四聚体全酶，由一组两个调节亚基（PKA-R）和两个催化亚基（PKA-C）组成。PKA-R 亚基作为 cAMP 的传感器并允许 PKA-C 活性。在哺乳动物精子获能过程中观察到的最早的信号事件之一是 PKA 的激活。因此，了解 PKA 活性如何在空间和时间上受到限制对于破译精子获能的关键步骤至关重要。人们普遍认为，PKA 的特异性取决于几个调节水平。锚定蛋白在实现适当的定位信号、亚细胞靶向和 cAMP 微区方面起着关键作用。这些多因素调节步骤对于 PKA 的精确时空激活是必要的。在这里，我们讨论了 PKA 在哺乳动物精子中的调节机制的最新理解，例如翻译后修饰，以及其作为有利于获能的分子事件的主调控因子的作用。
