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Spata6 is required for normal assembly of the sperm connecting piece and tight head–tail conjunction

  1. Wei Yana,c,1
  1. aDepartment of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557;
  2. bInstitute for Biogenesis Research, Department of Anatomy, Physiology, and Biochemistry, University of Hawaii Medical School, Honolulu, HI 96822; and
  3. cDepartment of Biology, University of Nevada, Reno, Reno, NV 89557

  1. Contributed by Ryuzo Yanagimachi, December 24, 2014 (sent for review October 23, 2014)

Significance

Male 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.

Abstract

“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).

Footnotes

  • ↵1To whom correspondence may be addressed. Email: yana{at}hawaii.edu or wyan{at}medicine.nevada.edu.

  • Author contributions: S.Y., R.Y., and W.Y. designed research; S.Y., C.J.S., J.B., H.Z., and B.P.B. performed research; R.Y. contributed new reagents/analytic tools; S.Y., C.J.S., J.B., H.Z., B.P.B., R.Y., and W.Y. analyzed data; and S.Y., R.Y., and W.Y. wrote the paper.

  • The authors declare no conflict of interest.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1424648112/-/DCSupplemental.

Freely available online through the PNAS open access option.

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