2012年12月3日，北京生命科学研究所王晓晨实验室和张宏实验室合作在 Development 杂志在线发表题为 Residual body removal during spermatogenesis in C. elegans requires genes that mediate cell corpse clearance 的文章。文中报道了线虫精子发育过程中残余体清除的分子机制。
在哺乳动物精子发育过程中，大部分细胞质被分离形成残余体，残余体脱离精子进而被降解。然而降解残余体的具体分子细胞机制并未被解析。在这篇文章中，我们发现秀丽线虫精子发育过程中产生的残余体被性腺鞘细胞吞入并降解。参与凋亡细胞降解的一系列基因同时调控残余体的清除。清除凋亡细胞的两条冗余信号通路通过识别残体表面的”eat me”信号磷脂酰丝氨酸参与了残余体的吞噬。包裹残余体的吞噬小体通过动态包被PtdIns(3)P，招募RAB小GTP水解酶等一系列过程完成成熟。雌雄同体线虫残余体的清除与凋亡细胞的清除有非常相似的过程，而雄性线虫残余体的清除所需吞噬基因及信号通路的组成则有所不同。残余体的高效清除保证了精子的数目和交配过程中精子的有效输出。我们的研究表明秀丽线虫精子发育过程中产生的残余体通过与凋亡细胞相同的吞噬降解通路被清除。该研究解析了精子发育过程中残余体清除的分子机制并提供了除凋亡细胞外探索吞噬通路分子机制的新的遗传模型。
张宏实验室与北大医学部联合培养的博士生黄洁与王晓晨实验室的博士生王海彬为本文共同第一作者，张宏博士和王晓晨博士为本文共同通讯作者。该项研究由国家基础研究基金973、科技部863计划和北京市科委资助，张宏博士和王晓晨博士的研究获得HHMI国际青年科学家奖支持，在中科院生物物理所和北京生命科学研究所完成。（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.
