Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
J Cell Sci. 2024 Aug 15;137(16). doi: 10.1242/jcs.261962. Epub 2024 Aug 29.
The structure of the sperm flagellar axoneme is highly conserved across species and serves the essential function of generating motility to facilitate the meeting of spermatozoa with the egg. During spermiogenesis, the axoneme elongates from the centrosome, and subsequently the centrosome docks onto the nuclear envelope to continue tail biogenesis. Mycbpap is expressed predominantly in mouse and human testes and conserved in Chlamydomonas as FAP147. A previous cryo-electron microscopy analysis has revealed the localization of FAP147 to the central apparatus of the axoneme. Here, we generated Mycbpap-knockout mice and demonstrated the essential role of Mycbpap in male fertility. Deletion of Mycbpap led to disrupted centrosome-nuclear envelope docking and abnormal flagellar biogenesis. Furthermore, we generated transgenic mice with tagged MYCBPAP, which restored the fertility of Mycbpap-knockout males. Interactome analyses of MYCBPAP using Mycbpap transgenic mice unveiled binding partners of MYCBPAP including central apparatus proteins, such as CFAP65 and CFAP70, which constitute the C2a projection, and centrosome-associated proteins, such as CCP110. These findings provide insights into a MYCBPAP-dependent regulation of the centrosome-nuclear envelope docking and sperm tail biogenesis.
精子鞭毛轴丝的结构在物种间高度保守，对于产生运动能力以促进精子与卵子的相遇至关重要。在精子发生过程中，轴丝从中心体伸长，随后中心体与核膜对接，以继续尾巴的发生。Mycbpap 在小鼠和人类睾丸中表达丰富，在衣藻中保守为 FAP147。先前的低温电子显微镜分析显示 FAP147 定位于轴丝的中心装置。在这里，我们生成了 Mycbpap 敲除小鼠，并证明了 Mycbpap 在雄性生育力中的重要作用。Mycbpap 的缺失导致中心体-核膜对接中断和鞭毛发生异常。此外，我们生成了带有标记 MYCBPAP 的转基因小鼠，该小鼠恢复了 Mycbpap 敲除雄性的生育能力。使用 Mycbpap 转基因小鼠的 MYCBPAP 相互作用组分析揭示了 MYCBPAP 的结合伙伴，包括中央装置蛋白，如 CFAP65 和 CFAP70，它们构成 C2a 突起，以及中心体相关蛋白，如 CCP110。这些发现为 MYCBPAP 依赖的中心体-核膜对接和精子尾巴发生的调控提供了新的认识。
