2012年12月3日,，北京生命科學(xué)研究所王曉晨實(shí)驗(yàn)室和張宏實(shí)驗(yàn)室合作在 Development 雜志在線發(fā)表題為 Residual body removal during spermatogenesis in C. elegans requires genes that mediate cell corpse clearance 的文章,。文中報(bào)道了線蟲精子發(fā)育過程中殘余體清除的分子機(jī)制。
在哺乳動物精子發(fā)育過程中,，大部分細(xì)胞質(zhì)被分離形成殘余體,，殘余體脫離精子進(jìn)而被降解。然而降解殘余體的具體分子細(xì)胞機(jī)制并未被解析,。在這篇文章中,，我們發(fā)現(xiàn)秀麗線蟲精子發(fā)育過程中產(chǎn)生的殘余體被性腺鞘細(xì)胞吞入并降解。參與凋亡細(xì)胞降解的一系列基因同時(shí)調(diào)控殘余體的清除,。清除凋亡細(xì)胞的兩條冗余信號通路通過識別殘?bào)w表面的”eat me”信號磷脂酰絲氨酸參與了殘余體的吞噬,。包裹殘余體的吞噬小體通過動態(tài)包被PtdIns(3)P，招募RAB小GTP水解酶等一系列過程完成成熟,。雌雄同體線蟲殘余體的清除與凋亡細(xì)胞的清除有非常相似的過程,，而雄性線蟲殘余體的清除所需吞噬基因及信號通路的組成則有所不同。殘余體的高效清除保證了精子的數(shù)目和交配過程中精子的有效輸出,。我們的研究表明秀麗線蟲精子發(fā)育過程中產(chǎn)生的殘余體通過與凋亡細(xì)胞相同的吞噬降解通路被清除,。該研究解析了精子發(fā)育過程中殘余體清除的分子機(jī)制并提供了除凋亡細(xì)胞外探索吞噬通路分子機(jī)制的新的遺傳模型。
張宏實(shí)驗(yàn)室與北大醫(yī)學(xué)部聯(lián)合培養(yǎng)的博士生黃潔與王曉晨實(shí)驗(yàn)室的博士生王海彬?yàn)楸疚墓餐谝蛔髡?，張宏博士和王曉晨博士為本文共同通訊作者,。該?xiàng)研究由國家基礎(chǔ)研究基金973、科技部863計(jì)劃和北京市科委資助,，張宏博士和王曉晨博士的研究獲得HHMI國際青年科學(xué)家獎(jiǎng)支持,，在中科院生物物理所和北京生命科學(xué)研究所完成。（生物谷Bioon.com）
doi: 10.1242/dev.086769.
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Residual body removal during spermatogenesis in C. elegans requires genes that mediate cell corpse clearance
Huang J, Wang H, Chen Y, Wang X, Zhang H.
Generation of spermatozoa involves segregation of most of the cytoplasm into residual bodies, which are detached from spermatids and eliminated in mammals. However, the molecular and cellular mechanism underlying the removal of residual bodies remains largely unknown. Here, we demonstrate that during C. elegans spermatogenesis residual bodies are engulfed and degraded by gonadal sheath cells, a process that uses the same set of genes underlying apoptotic cell removal. The two partially redundant engulfment pathways that clear cell corpses also mediate phagocytosis of residual bodies, possibly by recognizing the 'eat me' signal phosphatidylserine exposed on the surface. The residual body-containing phagosome undergoes a maturation process involving sequential steps including dynamic coating with PtdIns(3)P and association of RAB small GTPases. The genetic hierarchy of residual body removal in hermaphrodites is similar to that of cell corpse clearance, but male residual body removal involves a distinct hierarchy, with differential use of the engulfment genes. Efficient removal of residual bodies regulates the number of spermatids and effective transfer of spermatids during male matings. Our results indicate that a similar molecular mechanism is employed for the removal of residual bodies and apoptotic cell corpses in C. elegans.
