2012年6月,，BBA - Molecular and Cell Biology of Lipids雜志發(fā)表了中國科學(xué)院生物物理研究所苗龍課題組最新研究成果：Cholesterol and the biosynthesis of glycosphingolipids are required for sperm activation in Caenorhabditis elegans。該研究揭示出在精子活化早期,，膽固醇與糖鞘脂形成的脂筏結(jié)構(gòu)域參與了秀麗線蟲精子細胞成熟的信號轉(zhuǎn)導(dǎo),。
有性生殖的受精是一個復(fù)雜的分子事件,。對于哺乳動物而言，進入雌性生殖道的精子細胞并不具備受精能力,，必需在雌性生殖道內(nèi)經(jīng)過一段時間,，發(fā)生生理與形態(tài)學(xué)的變化才能獲得受精能力，這一過程被稱之為精子獲能,。精子獲能主要是精子細胞質(zhì)膜蛋白發(fā)生多種分子變化和膽固醇的流失從而改變精子質(zhì)膜的通透性與流動性,，導(dǎo)致鈣離子的流入，引起蛋白激酶的激活從而激活精子,。
秀麗線蟲是研究人類疾病分子機理的模式生物,。與哺乳動物精子不同，線蟲精子細胞以偽足的爬行取代鞭毛運動。然而,，與高等動物的精子獲能相似,，線蟲精子也需要一個精子活化的過程之后才具備受精能力。前期研究認為,，由于線蟲不具備膽固醇的生物合成途徑,，線蟲的存活需攝入外源膽固醇；且膽固醇在線蟲細胞中的含量極低,，膽固醇被認為僅僅是其它信號分子的前體,，而不是類似在高等動物中與糖鞘脂等在質(zhì)膜上形成的脂筏結(jié)構(gòu)域參與信號轉(zhuǎn)導(dǎo)。
作者研究發(fā)現(xiàn),，膽固醇在線蟲精子細胞質(zhì)膜上高度富集,。與高等動物的精子成熟類似，線蟲的精子活化也伴隨著質(zhì)膜中膽固醇的流失,。研究表明,，細胞質(zhì)膜中的膽固醇的存在對精子細胞的活化至關(guān)重要，揭示膽固醇在精子細胞質(zhì)膜中可能形成脂筏微結(jié)構(gòu)域參與精子細胞成熟過程中信號分子的篩選與信號轉(zhuǎn)導(dǎo),。進一步研究發(fā)現(xiàn),，影響參與脂筏微結(jié)構(gòu)域穩(wěn)定性的其它標志物，如糖基化磷脂酰肌醇錨定蛋白或糖鞘脂,，均可導(dǎo)致線蟲精子細胞活化與細胞遷移運動異常,。
生物物理所博士后竇江麗博士為本文第一作者。參與此工作的還有生物物理所的陳聯(lián)萬和博士生胡攸喬,，苗龍博士是本文通訊作者,。此項研究為科技部國家重點基礎(chǔ)研究973計劃和國家自然科學(xué)基金委員會資助。（生物谷Bioon.com）
doi:10.1016/j.bbalip.2012.03.005
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Cholesterol and the biosynthesis of glycosphingolipids are required for spermactivation in Caenorhabditiselegans
Jiangli Dou, Lianwan Chen, Youqiao Hu, Long Miao,
Ejaculated mammalian sperm must acquire fertilization capacity after residing into the female reproductive tract, a process collectively known as capacitation. Cholesterol efflux was required for sperm maturation. Different from flagellated sperm, C. eleganssperm are crawling cells. C. eleganssperm are highly enriched with cholesterol though this animal species lacks biosynthetic pathway for cholesterol and its survival requires an exogenous cholesterol supply. The low abundance of cholesterol in C. elegans lipid extract is thought insufficient to form lipid microdomains ubiquitously in this organism. We present evidence that cholesterol is enriched in the plasma membrane of C. elegans spermatids and that cholesterol- and glycosphingolipids (GSLs)-enriched membrane microdomains (lipid microdomains) mediate spermactivation. Disruption of sperm lipid microdomains by acute manipulation of cholesterol in vitro blocks the spermactivation. Restriction of cholesterol uptake also results in the abnormal spermactivation in both males and hermaphrodites. Manipulation of the integrity of lipid microdomains by targeting the biosynthesis of GSLs inhibits spermactivation and the inhibition can be rescued by the addition of exogenous GSLs. The cleavage of glycosylphosphatidylinositol (GPI)-anchored proteins, which are exclusively found in lipid microdomains, also affects spermactivation. We conclude that localized signaling mediated by lipid microdomains is critical for worm spermactivation. Lipid microdomains composed of cholesterol and GSLs have been observed in flagellated sperm of several animal species, thus cholesterol, before its efflux from the plasma membrane, might be needed to assemble into a platform for some more important upstream signal sorting during spermatogenesis than was previously thought.
