Key Laboratory for Regenerative Medicine (JNU-CUHK), Ministry of Education, Department of Developmental and Regenerative Biology, College of Life Science and Technologies, Jinan University, Guangzhou, P.R. China.
Department of Anesthesia, The First Affiliated Hospital, Jinan University, Guangzhou, P.R. China.
J Cell Biochem. 2018 Jun;119(6):4760-4774. doi: 10.1002/jcb.26668. Epub 2018 Mar 1.
The epididymis performs an important role in the maturation of spermatozoa including their acquisition of progressive motility and fertilizing ability. However, the molecular mechanisms that govern these maturational events are still poorly defined. Here we report that Clpsl2, a novel colipase homology, is exclusively expressed in the caupt epididymis and conserved in mammalian. Clpsl2 was secreted into the lumen and covered the acrosome region and principal piece of spermatozoa tail. And during epididymal transit, the binding rate between Clpsl2 protein and the spermatozoa gradually decreased. Though Clpsl2 had the highest identifies with pancreatic colipase (Clps), Clpsl2 lacked those conserved amino acids in pancreatic Clps that interacting with lipase, correspondingly, the recombinant Clpsl2 protein did not possess the Clps function such as promoting the hydrolysis of lipase to its substrate glycerine trioleate. However, sequence analysis showed that Clpsl2 has the potency to bind with lipid. Knockdown expression of Clpsl2 by lentivirus-mediated RNAi in vivo caused an attenuation of spermatozoa motility, a suppressed acrosomal reaction, a decrease of cauda spermatozoa number, and subfertility. This study identified a novel and conserved molecule, Clpsl2, was specifically expressed in epididymis and involved in the regulation of spermatozoa motility, acrosomal integrity, and male fertility.
附睾在精子成熟过程中发挥着重要作用，包括获得渐进性运动和受精能力。然而，调控这些成熟事件的分子机制仍不清楚。在这里，我们报告 Clpsl2 是一种新的脂肪酶辅因子同源物，它仅在附睾的主部中表达，并且在哺乳动物中保守。Clpsl2 被分泌到管腔中，覆盖精子的顶体区域和尾部主段。并且在附睾转运过程中，Clpsl2 蛋白与精子的结合率逐渐降低。尽管 Clpsl2 与胰腺脂肪酶辅因子 (Clps) 具有最高的相似度，但 Clpsl2 缺乏与脂肪酶相互作用的那些保守氨基酸，相应地，重组 Clpsl2 蛋白不具有 Clps 促进脂肪酶水解其底物甘油三油酸酯的功能。然而，序列分析表明 Clpsl2 具有与脂质结合的能力。体内通过慢病毒介导的 RNAi 敲低 Clpsl2 的表达导致精子运动减弱、顶体反应受到抑制、尾部精子数量减少和生育力下降。这项研究鉴定了一种新的和保守的分子，Clpsl2，它在附睾中特异性表达，参与调控精子的运动、顶体的完整性和雄性的生育能力。
