期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：5
页码：E430-E439
DOI：10.1073/pnas.1424648112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceMale infertility due to acephalic spermatozoa has been reported in both animals and humans, but its cause remains largely unknown. Here we report that inactivation of Spata6, an evolutionarily conserved gene, in mice leads to failure in development of the connecting piece during late spermiogenesis, along with production of headless spermatozoa in the epididymis and ejaculates. The defects may be ascribed to the disrupted myosin-based microfilament transport mediated by SPATA6 through its interactions with myosin light-chain and heavy-chain subunits. This study not only unveils the process of sperm neck formation at both the ultrastructural and molecular levels, but also provides a genetic basis for the production of acephalic spermatozoa in both humans and animals. "Pinhead sperm," or "acephalic sperm," a type of human teratozoospermia, refers to the condition in which ejaculate contains mostly sperm flagella without heads. Family clustering and homogeneity of this syndrome suggests a genetic basis, but the causative genes remain largely unknown. Here we report that Spata6, an evolutionarily conserved testis-specific gene, encodes a protein required for formation of the segmented columns and the capitulum, two major structures of the sperm connecting piece essential for linking the developing flagellum to the head during late spermiogenesis. Inactivation of Spata6 in mice leads to acephalic spermatozoa and male sterility. Our proteomic analyses reveal that SPATA6 is involved in myosin-based microfilament transport through interaction with myosin subunits (e.g., MYL6).
