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首页> 外文期刊>Journal of Cell Science >MRP4-mediated cAMP efflux is essential for mouse spermatozoa capacitation
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MRP4-mediated cAMP efflux is essential for mouse spermatozoa capacitation

机译：MRP4介导的CAMP EFFLUX对于小鼠精子的电容至关重要

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摘要

Mammalian spermatozoa must undergo biochemical and structural changes to acquire the capacity for fertilization, in a process known as capacitation. Activation of PKA enzymes is essential for capacitation, and thus cAMP levels are tightly regulated during this process. Previously, we demonstrated that during capacitation, bovine spermatozoa extrude cAMP through multidrug resistance-associated protein 4 (MRP4, also known as ABCC4), which regulates intracellular levels of the nucleotide and provides cAMP to the extracellular space. Here, we report the presence of functional MRP4 in murine spermatozoa, since its pharmacological inhibition with MK571 decreased levels of extracellular cAMP. This also produced a sudden increase in PKA activity, with decreased tyrosine phosphorylation at the end of capacitation. Blockade of MRP4 inhibited induction of acrosome reaction, hyperactivation and in vitro fertilization. Moreover, MRP4 inhibition generated an increase in Ca2+ levels mediated by PKA, and depletion of Ca2+ salts from the medium prevented the loss of motility and phosphotyrosine inhibition produced by MK571. These results were supported using spermatozoa from CatSper Ca2+ channel knockout mice. Taken together, these results suggest that cAMP efflux via MRP4 plays an essential role in mouse sperm capacitation.
机译：哺乳动物精子必须经历生化和结构性变化，以获得施肥能力，以称为容量的过程。 PKA酶的激活对于电容是必不可少的，因此在此过程中，CAMP水平紧密调节。以前，我们证明，在电容过程中，通过多药抗性相关蛋白4（MRP4，也称为ABCC4）的牛精子挤出阵营，其调节核苷酸的细胞内水平，并为细胞外空间提供营地。在这里，我们报告了鼠精子的功能性MRP4的存在，因为其药理学抑制与MK571的药物抑制降低，细胞外营的水平降低。这也产生了PKA活性的突然增加，在电容结束时，酪氨酸磷酸化降低。阻断MRP4抑制诱导肌肤反应，血管活化和体外施肥。此外，MRP4抑制产生了PKA介导的Ca2 +水平的增加，并且来自培养基的Ca2 +盐的耗尽可防止由MK571产生的运动性和磷酸酪氨酸抑制的损失。使用来自Catsper Ca2 +通道敲除小鼠的精子支持这些结果。总之，这些结果表明，通过MRP4的营地流出在小鼠精子的电容中起着重要作用。

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  • 来源
    《Journal of Cell Science》 |2019年第14期|共11页
  • 作者

    Alonso C. A. I.; Lottero-Leconte R.; Luque G. M.; Vernaz Z. J.; Di Siervi N.; Gervasi M. G.; Buffone M. G.; Davio C.; Perez-Martinez S.;

  • 作者单位

    Univ Buenos Aires Ctr Estudios Farmacol &

    Bot CEFYBO CONICET Fac Med C1121ABG Buenos Aires DF;

    Univ Buenos Aires Ctr Estudios Farmacol &

    Bot CEFYBO CONICET Fac Med C1121ABG Buenos Aires DF;

    Consejo Nacl Invest Cient &

    Tecn IBYME C1428ADN Buenos Aires DF Argentina;

    Univ Buenos Aires Ctr Estudios Farmacol &

    Bot CEFYBO CONICET Fac Med C1121ABG Buenos Aires DF;

    Univ Buenos Aires Inst Invest Farmacol ININFA CONICET Fac Farm &

    Bioquim C1113AAD Buenos Aires;

    Univ Massachusetts Dept Vet &

    Anim Sci Amherst MA 01003 USA;

    Consejo Nacl Invest Cient &

    Tecn IBYME C1428ADN Buenos Aires DF Argentina;

    Univ Buenos Aires Inst Invest Farmacol ININFA CONICET Fac Farm &

    Bioquim C1113AAD Buenos Aires;

    Univ Buenos Aires Ctr Estudios Farmacol &

    Bot CEFYBO CONICET Fac Med C1121ABG Buenos Aires DF;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    cAMP efflux; ABCC4; MRP4; PKA activity; Ca2+; Sperm capacitation; Mouse;

    机译：营地流出;ABCC4;MRP4;PKA活动;CA2 +;精子容量;小鼠;

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