Epididymosomes: transfer of fertility-modulating proteins to the sperm surface.
Epididymosomes: transfer of fertility-modulating proteins to the sperm surface.
复制标题
DOI：
10.4103/1008-682x.155538
复制
发表时间：
2015-09
影响因子：
2.9
通讯作者：
Martin-DeLeon PA
中科院分区：
文献类型：
--
作者：
Martin-DeLeon PA
在精子成熟过程中，从附睾腔液(ELF)中获得多种糖基磷脂酰肌醇(GPI)连接蛋白。这些蛋白质在免疫保护和受精的关键步骤中发挥作用，如获能、顶体胞吐和精子-卵子相互作用。它们在精子细胞上的获取既通过膜小泡(附睾体，EP)(首次报道停靠在精子表面)，也通过脂质载体促进与ELF的无膜部分相关的蛋白质的转移。虽然非囊泡部分的效率更高，但这两条途径都依赖于GPI锚点和精子表面外部脂层之间的疏水相互作用。最近的蛋白质组学和假说驱动的研究表明，几种哺乳动物的EP携带跨膜(TM)蛋白，包括质膜钙-ATPase 4(PMCA4)。PMCA4在睾丸合成，是一种重要的蛋白质，也是小鼠精子内钙离子外流的主要泵。在附睾期和体外，将PMCA4从牛和小鼠的EP传递到精子，表明EP在融合之前对接在精子表面，实验证据支持TM蛋白的融合机制。融合是由CD9促进的，CD9在膜上产生融合活性位点。根据PMCA4的S相互作用伙伴的知识，已经确定或预测在附睾体向精子递送的货物中存在许多TM和膜相关蛋白。这些在蛋白质组学研究中未被发现的钙依赖蛋白，在精子活力和受精率中发挥着重要作用，它们的检测突显了假设驱动方法的有效性。
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 Ca2+-ATPase 4 (PMCA4). Synthesized in the testis, PMCA4 is an essential protein and the major Ca2+ 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 Ca2+-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.