8月5日,，英國(guó)Journal of Cell Science雜志在線刊發(fā)了中國(guó)科學(xué)院上海生命科學(xué)研究院生物化學(xué)與細(xì)胞生物學(xué)研究所丁小燕研究組的工作,發(fā)現(xiàn)了一個(gè)在小鼠精子頂體發(fā)育過(guò)程中專一性表達(dá)的新的內(nèi)翻酶FetA，利用內(nèi)翻酶缺陷的酵母系統(tǒng)測(cè)定了它的翻轉(zhuǎn)不同種類磷脂的活性,，并進(jìn)一步探討了FetA在細(xì)胞的膜泡分泌中的功能,。上述研究成果得到同行評(píng)審專家和雜志編輯的高度贊賞,，該論文同時(shí)被9月1日出版的Development雜志推薦為值得關(guān)注的論文。
磷脂是生物膜的重要組分,，各種磷脂不對(duì)稱性地分布在生物膜雙層上,。氨酰甘油磷脂分布在質(zhì)膜的內(nèi)側(cè)面,，而中性磷脂集中在膜的外側(cè)面。內(nèi)翻酶（flippase）是負(fù)責(zé)將磷脂從質(zhì)膜的外側(cè)面轉(zhuǎn)運(yùn)到內(nèi)側(cè)面的一類代謝酶,。目前已知P4-ATPase家族成員具有內(nèi)翻酶活性,，但是這類酶在真核細(xì)胞尤其是高等動(dòng)物的生命活動(dòng)中的功能在很大程度上是不清楚的，對(duì)于在精子發(fā)生過(guò)程中是否有作用還完全沒有研究,。
生化與細(xì)胞所博士生徐鵬等人發(fā)現(xiàn)了P4-ATPase家族有一個(gè)新的成員，命名其為FetA,。表達(dá)譜分析表明FetA特異地表達(dá)在睪丸組織,，用制備的特異性抗體染色結(jié)果表明FetA在精子發(fā)生過(guò)程中始終定位在頂體中。通過(guò)將FetA轉(zhuǎn)化到內(nèi)翻酶缺失的酵母菌株中,，作者證明了FetA具有內(nèi)翻磷脂酰乙醇胺（PE）和磷脂酰膽堿（PC）的活性,。功能缺失研究結(jié)果發(fā)現(xiàn)，F(xiàn)etA缺失可導(dǎo)致 細(xì)胞的高爾基體形態(tài)異常從而影響細(xì)胞的分泌活動(dòng),。該論文發(fā)現(xiàn)了一種新的頂體內(nèi)翻酶,，為進(jìn)一步研究真核生物膜磷脂的不對(duì)稱性分布的機(jī)理以及哺乳動(dòng)物精子的頂體形成打下了堅(jiān)實(shí)的基礎(chǔ)。
該項(xiàng)研究工作得到了國(guó)家科技部,、基金委,、中國(guó)科學(xué)院的經(jīng)費(fèi)支持，部分工作與德國(guó)洪堡大學(xué)生物學(xué)研究所Thomas Guenther Pomorski教授研究組合作完成,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
