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赖氨酸乙酰化修饰调节小鼠精子获能。

Lysine acetylation modulates mouse sperm capacitation.

机构信息

Laboratory of Cell Signal Transduction Networks, Instituto de Biología Molecular y Celular de Rosario (IBR), CONICET-UNR, Rosario, 2000, Argentina.

Laboratory of Cellular and Molecular Reproductive Biology, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, C1428ADN, Argentina.

出版信息

Sci Rep. 2018 Sep 6;8(1):13334. doi: 10.1038/s41598-018-31557-5.

Abstract

Mammalian sperm are unable to fertilize the egg immediately after ejaculation. To gain fertilization competence, they need to undergo a series of modifications inside the female reproductive tract, known as capacitation. Capacitation involves several molecular events such as phosphorylation cascades, hyperpolarization of the plasma membrane and intracellular Ca changes, which prepare the sperm to develop two essential features for fertilization competence: hyperactivation and acrosome reaction. Since sperm cells lack new protein biosynthesis, post-translational modification of existing proteins plays a crucial role to obtain full functionality. Here, we show the presence of acetylated proteins in murine sperm, which increase during capacitation. Pharmacological hyperacetylation of lysine residues in non-capacitated sperm induces activation of PKA, hyperpolarization of the sperm plasma membrane, CatSper opening and Ca influx, all capacitation-associated molecular events. Furthermore, hyperacetylation of non-capacitated sperm promotes hyperactivation and prepares the sperm to undergo acrosome reaction. Together, these results indicate that acetylation could be involved in the acquisition of fertilization competence of mammalian sperm.

摘要

哺乳动物精子在射精后不能立即使卵子受精。为了获得受精能力,它们需要在雌性生殖道内经历一系列的修饰,称为获能。获能涉及几个分子事件,如磷酸化级联、质膜超极化和细胞内 Ca 变化,这些事件使精子具备了进行受精的两个必要特征:超激活和顶体反应。由于精子细胞缺乏新的蛋白质合成,因此现有蛋白质的翻译后修饰对于获得完全的功能至关重要。在这里,我们发现在小鼠精子中存在乙酰化蛋白,这些蛋白在获能过程中增加。在未获能的精子中,赖氨酸残基的药物诱导超乙酰化会诱导 PKA 的激活、精子质膜的超极化、CatSper 的开放和 Ca 内流,所有这些都是与获能相关的分子事件。此外,非获能精子的超乙酰化会促进超激活,并使精子准备好进行顶体反应。综上所述,这些结果表明,乙酰化可能参与了哺乳动物精子受精能力的获得。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0c/6127136/a80e1ce41402/41598_2018_31557_Fig1_HTML.jpg

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