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Ceramide induces a multicomponent intracellular calcium increase triggering the acrosome secretion in human sperm.
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ( IF 4.6 ) Pub Date : 2020-03-17 , DOI: 10.1016/j.bbamcr.2020.118704
Cintia Celina Vaquer 1 , Laila Suhaiman 2 , Martín Alejandro Pavarotti 1 , Gerardo Andrés De Blas 3 , Silvia Alejandra Belmonte 3
Affiliation  

Exocytosis of spermatozoon's secretory vesicle, named acrosome reaction (AR), is a regulated event that plays a central role in fertilization. It is coupled to a complex calcium signaling. Ceramide is a multitasking lipid involved in exocytosis. Nevertheless, its effect on secretion is controversial and the underlying cellular and molecular mechanisms remain unknown. Human spermatozoa are useful to dissect the role of ceramide in secretion given that the gamete is not capable to undergo any trafficking mechanisms other than exocytosis. We report for the first time, the presence of sphingolipid metabolism enzymes such as neutral-sphingomyelinase and ceramide synthase in sperm. Ceramidases are also present and active. Both the addition of cell-permeable ceramide and the rise of the endogenous one, increase intracellular calcium acting as potent inducers of exocytosis. Ceramide triggers AR in capacitated spermatozoa and enhances the gamete response to progesterone. The lipid induces physiological ultrastructural changes in the acrosome and triggers an exocytosis-signaling cascade involving protein tyrosine phosphatase 1B and VAMP2. Real-time imaging showed an increment of calcium in the cytosol upon ceramide treatment either in the absence or in the presence of extracellular calcium. Pharmacological experiments demonstrate that at early stages the process involves ryanodine receptors, CatSper (calcium channel of sperm), and store-operated calcium channels. We set out the signaling sequence of events that connect ceramide to internal calcium mobilization and external calcium signals during secretion. These results allow the coordination of lipids and proteins in a pathway that accomplishes secretion. Our findings contribute to the understanding of ceramide's role in regulated exocytosis and fertilization.

中文翻译:

神经酰胺诱导细胞内钙的多组分增加,从而触发人类精子中顶体的分泌。

精子分泌囊泡的胞吐作用称为顶体反应(AR),是受调节的事件,在受精过程中起核心作用。它与复杂的钙信号传导耦合。神经酰胺是参与胞吐作用的多任务脂质。然而,其对分泌的作用尚存争议,其潜在的细胞和分子机制仍然未知。鉴于配子除了胞吐作用以外没有其他任何运输机制,人类精子可用于解剖神经酰胺在分泌中的作用。我们首次报道了精子中鞘脂代谢酶的存在,例如中性鞘磷脂酶和神经酰胺合酶。陶瓷酶也存在并且活跃。细胞渗透性神经酰胺的添加和内源性神经酰胺的增加,增加细胞内钙作为胞吐作用的有效诱导剂。神经酰胺可触发精子中的AR,并增强配子对孕酮的反应。脂质诱导顶体中的生理超微结构变化,并触发涉及蛋白酪氨酸磷酸酶1B和VAMP2的胞吐信号级联反应。实时成像显示,在不存在或存在细胞外钙的情况下,神经酰胺处理后胞浆中钙的增加。药理实验表明,该过程在早期涉及到精氨酸受体,CatSper(精子的钙通道)和储存钙通道。我们列出了在分泌过程中将神经酰胺连接到内部钙动员和外部钙信号的事件的信号序列。这些结果允许脂质和蛋白质在完成分泌的途径中协调。我们的发现有助于理解神经酰胺在调控胞吐和受精中的作用。
更新日期:2020-04-20
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