Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.
Center for Experimental Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.
Mol Hum Reprod. 2024 Jun 26;30(7). doi: 10.1093/molehr/gaae022.
Acephalic spermatozoa syndrome (ASS) is a severe teratospermia with decaudated, decapitated, and malformed sperm, resulting in male infertility. Nuclear envelope protein SUN5 localizes to the junction between the sperm head and tail. Mutations in the SUN5 gene have been identified most frequently (33-47%) in ASS cases, and its molecular mechanism of action is yet to be explored. In the present study, we generated Sun5 knockout mice, which presented the phenotype of ASS. Nuclear membrane protein LaminB1 and cytoskeletal GTPases Septin12 and Septin2 were identified as potential partners for interacting with SUN5 by immunoprecipitation-mass spectrometry in mouse testis. Further studies demonstrated that SUN5 connected the nucleus by interacting with LaminB1 and connected the proximal centriole by interacting with Septin12. The binding between SUN5 and Septin12 promoted their aggregation together in the sperm neck. The disruption of the LaminB1/SUN5/Septin12 complex by Sun5 deficiency caused separation of the Septin12-proximal centriole from the nucleus, leading to the breakage of the head-to-tail junction. Collectively, these data provide new insights into the pathogenesis of ASS caused by SUN5 deficiency.
无头精子症（ASS）是一种严重的精子畸形症，其精子表现为断头、断尾和畸形，导致男性不育。核包膜蛋白 SUN5 定位于精子头部和尾部的连接处。SUN5 基因突变已在 ASS 病例中最常被发现（33-47%），其作用的分子机制仍有待探索。在本研究中，我们生成了 Sun5 敲除小鼠，其表现出 ASS 的表型。通过免疫沉淀-质谱法在小鼠睾丸中鉴定出核膜蛋白 laminB1 和细胞骨架 GTPases Septin12 和 Septin2 是与 SUN5 相互作用的潜在伴侣。进一步的研究表明，SUN5 通过与 laminB1 相互作用连接核，通过与 Septin12 相互作用连接近端中心粒。SUN5 与 Septin12 的结合促进了它们在精子颈部的聚集。Sun5 缺乏导致的 laminB1/SUN5/Septin12 复合物的破坏导致 Septin12-近端中心粒与核分离，从而导致头尾连接处断裂。总的来说，这些数据为 SUN5 缺乏导致 ASS 的发病机制提供了新的见解。
