The perinuclear theca (PT) is a cytoskeletal element encapsulating the sperm nucleus; however, physiological roles of PT in sperm are largely uncertain. Here, we revealed that ACTRT1, ACTRT2, ACTL7A, and ACTL9 proteins interact to form a multimeric complex and localize to the subacrosomal region of spermatids. Furthermore, we engineered Actrt1-knockout (KO) mice to define the functions of ACTRT1. Despite the normal sperm count and motility, Actrt1-KO males were severely subfertile due to a deficiency in fertilization. Loss of ACTRT1 caused a high incidence of malformed heads and detachment of acrosomes from sperm nuclei, which were caused by the loosened acroplaxome structure during spermiogenesis. Furthermore, Actrt1-KO sperm showed reduced ACTL7A and PLCζ protein content as a potential cause of fertilization defects. Moreover, we revealed that ACTRT1 anchors developing acrosomes to the nucleus, likely by interacting with the inner acrosomal membrane protein SPACA1 and the nuclear envelope proteins PARP11 and SPATA46. Loss of ACTRT1 weakened the interaction between ACTL7A and SPACA1. Our study and recent findings of ACTL7A/ACTL9-deficient sperm together reveal that the sperm PT-specific ARP complex mediates the acrosome-nucleus connection.
Loss of perinuclear theca ACTRT1 causes acrosome detachment and severe male subfertility
These authors contributed equally to this work.
- Award Group:
- Funder(s): National Key Research and Development Program of China
- Award Id(s): 2019YFA0802101
- Funder(s):
- Award Group:
- Funder(s): Fundamental Research Funds for the Central Universities
- Award Id(s): 2019NTST14
- Funder(s):
- Award Group:
- Funder(s): Open Fund of Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education
- Award Id(s): Su-Ren Chen
- Funder(s):
Currently Viewing Accepted Manuscript - Newer Version Available
Xiao-Zhen Zhang, Lin-Lin Wei, Xiao-Hui Zhang, Hui-Juan Jin, Su-Ren Chen; Loss of perinuclear theca ACTRT1 causes acrosome detachment and severe male subfertility. Development 2022; dev.200489. doi: https://doi.org/10.1242/dev.200489
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