Lysine glutarylation in human sperm is associated with progressive motility
Lysine glutarylation in human sperm is associated with progressive motility
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人类精子中的赖氨酸戊二酰化与渐进运动有关
DOI：
10.1093/humrep/dez068
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发表时间：
2019-07-01
影响因子：
6.1
通讯作者：
Luo, Tao
中科院分区：
文献类型：
--
作者：
Cheng, Yi-min;Hu, Xiao-nian;Luo, Tao
研究问题：赖氨酸戊二酰化（Kglu）这种新发现的蛋白质翻译后修饰（PTM）在人类 Fi 精子中是否起作用？总结答案：Kglu 存在于位于人类精子尾部的几种蛋白质中，在弱精子症（A）预兆中减少，并且与人类精子的前向运动呈正相关，表明其在精子活力中发挥重要作用。 维持精子活力。已知信息：由于成熟精子几乎转录沉默，PTM 被认为是调节精子功能的重要途径。然而，迄今为止，仅对成熟精子中的磷酸化进行了广泛研究。蛋白质赖氨酸修饰（PLM）作为 PTM 的热点，除了少数关于赖氨酸甲基化和乙酰化的报道外，研究很少。作为一种新发现的 PLM，Kglu 尚未得到很好的表征，特别是在成熟精子中。 研究设计、规模、持续时间：精子样本取自 2016 年 2 月至 2018 年 1 月期间访问生殖医学中心的正常精子 (N) 男性和 A 男性。总共招募了 61 名 N 男性和 59 名 A 男性参与该研究。 参与者/材料、设置、方法： 使用先前合格的泛抗戊二酰赖氨酸抗体通过免疫印迹和免疫荧光测定对 Kglu 进行检查，该抗体可识别多种序列背景（组蛋白和非组蛋白底物）中的戊二酰赖氨酸，但不识别结构相似的丙二酰赖氨酸和琥珀酰赖氨酸。使用激光扫描共焦显微镜和超分辨率结构照明显微镜对免疫荧光测定进行成像。通过计算机辅助精子分析检查精子活力参数。主要结果和机会的作用：Kglu存在于位于人类精子尾部的几种蛋白质（20-150 kDa）中，特别是在中段和主段的后部。精子 Kglu 受到类似于 HeLa 细胞中的调节系统（酶和戊二酰辅酶 A）的调节。与N型男性相比，A型男性的精子Kglu平均水平显着降低（P < 0.001），并且与前向运动力呈正相关（P < 0.001）。在精子中Kglu水平较低的A男性中，戊二酸钠诱导的Kglu水平升高显着改善了前向运动（P < 0.001）。此外，A 型男性精子 Kglu 水平的降低伴随着精子戊二酰辅酶 A 脱氢酶（Kglu 的一种调节酶）的增加。大规模数据：无限制，注意原因：虽然本研究表明精子 Kglu 参与维持人类精子的前向运动，但其潜在机制需要进一步研究。 研究结果的意义：本研究的结果深入了解了 Kglu 在人类精子中的新作用，并表明精子 PLM 异常可能是弱精子症的原因之一。
STUDY QUESTION: Is there a role for lysine glutarylation (Kglu), a newly identified protein post-translational modification (PTM), in human Fi sperm?SUMMARY ANSWER: Kglu occurs in several proteins located in the tail of human sperm, and it was reduced in asthenozoospermic (A) omen and positively correlated with progressive motility of human sperm, indicating its important role in maintaining sperm motility.WHAT IS KNOWN ALREADY: Since mature sperm are almost transcriptionally silent, PTM is regarded as an important pathway in regulating sperm function. However, only phosphorylation has been extensively studied in mature sperm to date. Protein lysine modification (PLM), a hot spot of PTMs, was rarely studied except for a few reports on lysine methylation and acetylation. As a newly identified PLM, Kglu has not been well characterized, especially in mature sperm.STUDY DESIGN, SIZE, DURATION: Sperm samples were obtained from normozoospermic (N) men and A men who visited the reproductive medical center between February 2016 and January 2018. In total, 61 N men and 59 A men were recruited to participate in the study.PARTICIPANTS/MATERIALS, SETTING, METHODS: Kglu was examined by immunoblotting and immunofluorescence assays using a previously qualified pan-anti-glutaryllysine antibody that recognizes glutaryllysine in a wide range of sequence contexts (both in histones and non-histone substrates) but not the structurally similar malonyllysine and succinyllysine. The immunofluorescence assay was imaged using laser scanning confocal microscopy and super-resolution structured illumination microscopy. Sperm motility parameters were examined by computer-assisted sperm analysis.MAIN RESULTS AND THE ROLE OF CHANCE: Kglu occurs in several proteins (20-150 kDa) located in the tail of human sperm, especially in the middle piece and the latter part of the principal piece. Sperm Kglu was modulated by regulatory systems (enzymes and glutarylCoA) similar to those in HeLa cells. The mean level of sperm Kglu was significantly reduced in A men compared with N men (P < 0.001) and was positively correlated with progressive motility (P < 0.001). The sodium glutarate-induced elevation of Kglu levels in A men with lower Kglu levels in sperm significantly improved the progressive motility (P < 0.001). Furthermore, the reduced sperm Kglu levels in A men was accompanied by an increase in sperm glutaryl-CoA dehydrogenase (a regulatory enzyme of Kglu).LARGE SCALE DATA: N/ALIMITATIONS, REASONS FOR CAUTION: Although the present study indicated the involvement of sperm Kglu in maintaining progressive motility of human sperm, the underlying mechanism needs to be investigated further.WIDER IMPLICATIONS OF THE FINDINGS: The findings of this study provide an insight into the novel role of Kglu in human sperm and suggest that abnormality of sperm PLMs may be one of the causes of asthenozoospermia.