• PMID: 29298896
• Gene Name: DNAJB13
• Condition: Acephalic spermatozoa, Male infertility
• Association: Associated
• Mutation: SUN5 mutation (c.475C?T; p.Arg159*)
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Acephalic spermatozoa, Male infertility

Mechanistic insights into acephalic spermatozoa syndrome-associated mutations in the human SUN5 gene

Shang Y, Yan J, Tang W, Liu C, Xiao S, Guo Y, Yuan L, Chen L, Jiang H, Guo X, Qiao J, Li W.

Acephalic spermatozoa syndrome has been reported for many decades; it is characterized by very few intact spermatozoa and tailless sperm heads in the semen and causes severe male infertility. The only gene in which mutations have been found to be associated with this syndrome encodes Sad1 and UNC84 domain-containing 5 (SUN5), a testis-specific nuclear envelope protein. The functional role of SUN5 has been well-studied in mouse models, but the molecular basis for the pathogenic effects of mutations in the human SUN5 gene remains elusive. Here, we report a new SUN5 mutation (c.475C→T; p.Arg159*), and explore the pathogenic effects of all known SUN5 mutations on acephalic spermatozoa syndrome. Using an artificial splicing system, we found that the intronic mutation affects the splicing of SUN5 mRNA, yielding a premature stop codon that results in a truncated SUN5 protein. We also found that SUN5 interacts with the coupling apparatus protein DnaJ heat shock protein family (Hsp40) member B13 (DNAJB13) during spermatogenesis, and the substitutions in the SUN5 SUN domain impair its interaction with DNAJB13. Furthermore, we observed that many SUN5 mutations affect the secondary structure of the protein and influence its folding and cellular localization. In summary, our findings indicate an interaction of SUN5 with DNAJB13 during spermatogenesis, provide mechanistic insights into the functional role of this interaction in sperm head-tail integration, and elucidate the molecular etiology of acephalic spermatozoa syndrome-associated SUN5 mutations. CI - © 2018 by The American Society for Biochemistry and Molecular Biology, Inc. FAU - Shang, Yongliang AU - Shang Y AD - From the State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. AD - the University of Chinese Academy of Sciences, Beijing 100049, China. FAU - Yan, Jie AU - Yan J AD - the Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China. FAU - Tang, Wenhao AU - Tang W AD - the Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China. FAU - Liu, Chao AU - Liu C AD - From the State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. AD - the University of Chinese Academy of Sciences, Beijing 100049, China. FAU - Xiao, Sai AU - Xiao S AD - From the State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. AD - the University of Chinese Academy of Sciences, Beijing 100049, China. FAU - Guo, Yueshuai AU - Guo Y AD - the State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Department of Histology and Embryology, Nanjing Medical University, Nanjing 21 0029, China. FAU - Yuan, Li AU - Yuan L AD - the Savaid School of Medicine, University of Chinese Academy of Sciences, Beijing 100049, China. FAU - Chen, Liang AU - Chen L AD - the Medical Center of Reproductive and Genetics, Peking University First Hospital, Beijing 100034, China, and. FAU - Jiang, Hui AU - Jiang H AD - the Department of Urology, Peking University Third Hospital, Beijing 100191, China. FAU - Guo, Xuejiang AU - Guo X AD - the State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Department of Histology and Embryology, Nanjing Medical University, Nanjing 21 0029, China. FAU - Qiao, Jie AU - Qiao J AD - the Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China, jie.qiao@263.net.