8月5日，英国Journal of Cell Science杂志在线刊发了中国科学院上海生命科学研究院生物化学与细胞生物学研究所丁小燕研究组的工作,发现了一个在小鼠精子顶体发育过程中专一性表达的新的内翻酶FetA，利用内翻酶缺陷的酵母系统测定了它的翻转不同种类磷脂的活性，并进一步探讨了FetA在细胞的膜泡分泌中的功能。上述研究成果得到同行评审专家和杂志编辑的高度赞赏，该论文同时被9月1日出版的Development杂志推荐为值得关注的论文。

磷脂是生物膜的重要组分，各种磷脂不对称性地分布在生物膜双层上。氨酰甘油磷脂分布在质膜的内侧面，而中性磷脂集中在膜的外侧面。内翻酶（flippase）是负责将磷脂从质膜的外侧面转运到内侧面的一类代谢酶。目前已知P4-ATPase家族成员具有内翻酶活性，但是这类酶在真核细胞尤其是高等动物的生命活动中的功能在很大程度上是不清楚的，对于在精子发生过程中是否有作用还完全没有研究。

生化与细胞所博士生徐鹏等人发现了P4-ATPase家族有一个新的成员，命名其为FetA。表达谱分析表明FetA特异地表达在睾丸组织，用制备的特异性抗体染色结果表明FetA在精子发生过程中始终定位在顶体中。通过将FetA转化到内翻酶缺失的酵母菌株中，作者证明了FetA具有内翻磷脂酰乙醇胺（PE）和磷脂酰胆碱（PC）的活性。功能缺失研究结果发现，FetA缺失可导致 细胞的高尔基体形态异常从而影响细胞的分泌活动。该论文发现了一种新的顶体内翻酶，为进一步研究真核生物膜磷脂的不对称性分布的机理以及哺乳动物精子的顶体形成打下了坚实的基础。

该项研究工作得到了国家科技部、基金委、中国科学院的经费支持，部分工作与德国洪堡大学生物学研究所Thomas Guenther Pomorski教授研究组合作完成。

原始出处：

Journal of Cell Science 122, 2866-2876 (2009)doi: 10.1242/10.1242/jcs.047423

Identification of a novel mouse P4-ATPase family member highly expressed during spermatogenesis

Peng Xu1,*, Juha Okkeri2,*,, Susanne Hanisch2,3, Rui-Ying Hu1, Qin Xu1, Thomas Günther Pomorski2,3, and Xiao-Yan Ding1,

1 Laboratory of Molecular Cell Biology, Key Laboratory of Stem Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China
2 Institute of Biology, Humboldt University Berlin, Invalidenstrasse 42, 10115 Berlin, Germany
3 Department of Plant Biology and Biotechnology, Faculty of Life Sciences, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark

P4-ATPases are transmembrane proteins unique to eukaryotes that play a fundamental role in vesicular transport. They have been proposed to act as phospholipid flippases thereby regulating lipid topology in cellular membranes. We cloned and characterized a novel murine P4-ATPase that is specifically expressed in testis, and named it FetA (flippase expressed in testis splicing form A). When expressed in Saccharomyces cerevisiae, FetA localizes partially to the plasma membrane resulting in increased internalization of NBD-labeled phosphatidylethanolamine and phosphatidylcholine, supporting a role for FetA in the inward lipid translocation across cellular membranes. In mouse testis, FetA protein is detected in gamete cells, from pachytene spermatocytes to mature sperms, and its intracellular localization is tightly related with acrosome formation, a process that involves intensive intracellular vesicle formation and fusion. Furthermore, loss-of-function of FetA by RNA interference in mastocytoma P815 cells profoundly perturbs the structural organization of the Golgi complex and causes loss of constitutive secretion at lower temperature. Our findings point to an essential role of FetA in Golgi morphology and secretory function, suggesting a crucial role for this novel murine P4-ATPase in spermatogenesis.