Martin-DeLeon Patricia A
Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
Asian J Androl. 2015 Sep-Oct;17(5):720-5. doi: 10.4103/1008-682X.155538.
A variety of glycosylphosphatidylinositol (GPI)-linked proteins are acquired on spermatozoa from epididymal luminal fluids (ELF) during sperm maturation. These proteins serve roles in immunoprotection and in key steps of fertilization such as capacitation, acrosomal exocytosis and sperm-egg interactions. Their acquisition on sperm cells is mediated both by membrane vesicles (epididymosomes, EP) which were first reported to dock on the sperm surface, and by lipid carriers which facilitate the transfer of proteins associated with the membrane-free fraction of ELF. While the nonvesicular fraction is more efficient, both pathways are dependent on hydrophobic interactions between the GPI-anchor and the external lipid layer of the sperm surface. More recently proteomic and hypothesis-driven studies have shown that EP from several mammals carry transmembrane (TM) proteins, including plasma membrane Ca 2 + -ATPase 4 (PMCA4). Synthesized in the testis, PMCA4 is an essential protein and the major Ca 2 + efflux pump in murine spermatozoa. Delivery of PMCA4 to spermatozoa from bovine and mouse EP during epididymal maturation and in vitro suggests that the docking of EP on the sperm surface precedes fusion, and experimental evidence supports a fusogenic mechanism for TM proteins. Fusion is facilitated by CD9, which generates fusion-competent sites on membranes. On the basis of knowledge of PMCA4's interacting partners a number of TM and membrane-associated proteins have been identified or are predicted to be present, in the epididymosomal cargo deliverable to spermatozoa. These Ca 2 + -dependent proteins, undetected in proteomic studies, play essential roles in sperm motility and fertility, and their detection highlights the usefulness of the hypothesis-driven approach.
在精子成熟过程中，多种糖基磷脂酰肌醇（GPI）连接蛋白从附睾管腔液（ELF）中获得并附着于精子上。这些蛋白在免疫保护以及受精的关键步骤中发挥作用，如获能、顶体胞吐和精卵相互作用。它们在精子细胞上的获得是由膜泡（附睾小体，EP）介导的，附睾小体首次被报道可停靠在精子表面，同时也由脂质载体介导，脂质载体促进了与ELF无膜部分相关蛋白的转移。虽然非囊泡部分更有效，但这两种途径都依赖于GPI锚与精子表面外部脂质层之间的疏水相互作用。最近的蛋白质组学和假说驱动研究表明，来自几种哺乳动物的EP携带跨膜（TM）蛋白，包括质膜Ca²⁺ -ATP酶4（PMCA4）。PMCA4在睾丸中合成，是小鼠精子中的一种必需蛋白和主要的Ca²⁺ 外流泵。在附睾成熟过程中以及体外，牛和小鼠的EP将PMCA4递送至精子，这表明EP在精子表面的停靠先于融合，并且实验证据支持TM蛋白的融合机制。CD9促进融合，它在膜上产生具有融合能力的位点。基于对PMCA4相互作用伙伴的了解，已鉴定出或预计在可递送至精子的附睾小体货物中存在一些TM和膜相关蛋白。这些在蛋白质组学研究中未检测到的Ca²⁺ 依赖性蛋白在精子运动和生育中起重要作用，它们的检测突出了假说驱动方法的有用性。
