Savaid Medical School, University of Chinese Academy of Sciences, Beijing, P.R. China.
Fertility Preservation Lab, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, P.R. China.
Nat Commun. 2021 Aug 13;12(1):4926. doi: 10.1038/s41467-021-25227-w.
The sperm head-to-tail coupling apparatus (HTCA) ensures sperm head-tail integrity while defective HTCA causes acephalic spermatozoa, rendering males infertile. Here, we show that CENTLEIN is indispensable for HTCA integrity and function, and that inactivation of CENTLEIN in mice leads to sperm decapitation and male sterility. We demonstrate that CENTLEIN directly interacts with both SUN5 and PMFBP1, two proteins localized in the HTCA and related with acephalic spermatozoa syndrome. We find that the absence of Centlein sets SUN5 and PMFBP1 apart, the former close to the sperm head and the latter in the decapitated tail. We show that lack of Sun5 results in CENTLEIN and PMFBP1 left in the decapitated tail, while disruption of Pmfbp1 results in SUN5 and CENTLEIN left on the detached sperm head. These results demonstrate that CENTLEIN cooperating with SUN5 and PMFBP1 participates in the HTCA assembly and integration of sperm head to the tail, indicating that impairments of CENTLEIN might be associated with acephalic spermatozoa syndrome in humans.
精子头对头连接装置（HTCA）可确保精子头部和尾部的完整性，而 HTCA 缺陷会导致无头精子，从而使男性不育。在这里，我们表明 CENTLEIN 对于 HTCA 的完整性和功能是不可或缺的，并且 CENTLEIN 在小鼠中的失活会导致精子断头和雄性不育。我们证明 CENTLEIN 可直接与 SUN5 和 PMFBP1 相互作用，这两种蛋白质定位于 HTCA 中，与无头精子综合征有关。我们发现 Centlein 的缺失会使 SUN5 和 PMFBP1 分开，前者靠近精子头部，后者位于断头尾部。我们表明，Sun5 的缺失会导致断头尾部残留 Centlein 和 PMFBP1，而 Pmfbp1 的破坏会导致 SUN5 和 CENTLEIN 残留在分离的精子头部上。这些结果表明，CENTLEIN 与 SUN5 和 PMFBP1 合作参与 HTCA 的组装和精子头部与尾部的整合，表明 CENTLEIN 的损伤可能与人类的无头精子综合征有关。
