SEPT12 orchestrates the formation of mammalian sperm annulus by organizing core octameric complexes with other SEPT proteins

Yung Che Kuo, Yi Ru Shen, Hau Inh Chen, Ying Hung Lin, Ya Yun Wang, Yet Ran Chen, Chia-Yih Wang, Pao-Lin Kuo

Research output: Contribution to journalArticle

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Abstract

Male infertility has become a worldwide health problem, but the etiologies of most cases are still unknown. SEPT12, a GTP-binding protein, is involved in male fertility. Two SEPT12 mutations (SEPT12T89M and SEPT12D197N) have been identified in infertile men who have a defective sperm annulus with a bent tail. The function of SEPT12 in the sperm annulus is still unclear. Here, we found that SEPT12 formed a filamentous structure with SEPT7, SEPT 6, SEPT2 and SEPT4 at the sperm annulus. The SEPT12- based septin core complex was assembled as octameric filaments comprising the SEPT proteins 12-7-6-2-2-6-7-12 or 12-7-6-4-4-6-7- 12. In addition, the GTP-binding domain of SEPT12 was crucial for its interaction with SEPT7, and the N- and C-termini of SEPT12 were required for the interaction of SEPT12 with itself to polymerize octamers into filaments. Mutant mice carrying the SEPT12D197N mutation, which disrupts SEPT12 filament formation, showed a disorganized sperm annulus, bent tail, reduced motility and loss of the SEPT ring structure at the sperm annulus. These phenotypes were also observed in an infertile man carrying SEPT12D197N. Taken together, our results demonstrate the molecular architecture of SEPT12 filaments at the sperm annulus, their mechanical support of sperm motility, and their correlation with male infertility.

Original languageEnglish
Pages (from-to)923-934
Number of pages12
JournalJournal of Cell Science
Volume128
Issue number5
DOIs
Publication statusPublished - 2015 Jan 1

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Spermatozoa
Proteins
Male Infertility
Tail
Septins
Mutation
Sperm Motility
Guanosine Triphosphate
GTP-Binding Proteins
Fertility
Phenotype

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Kuo, Yung Che ; Shen, Yi Ru ; Chen, Hau Inh ; Lin, Ying Hung ; Wang, Ya Yun ; Chen, Yet Ran ; Wang, Chia-Yih ; Kuo, Pao-Lin. / SEPT12 orchestrates the formation of mammalian sperm annulus by organizing core octameric complexes with other SEPT proteins. In: Journal of Cell Science. 2015 ; Vol. 128, No. 5. pp. 923-934.
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abstract = "Male infertility has become a worldwide health problem, but the etiologies of most cases are still unknown. SEPT12, a GTP-binding protein, is involved in male fertility. Two SEPT12 mutations (SEPT12T89M and SEPT12D197N) have been identified in infertile men who have a defective sperm annulus with a bent tail. The function of SEPT12 in the sperm annulus is still unclear. Here, we found that SEPT12 formed a filamentous structure with SEPT7, SEPT 6, SEPT2 and SEPT4 at the sperm annulus. The SEPT12- based septin core complex was assembled as octameric filaments comprising the SEPT proteins 12-7-6-2-2-6-7-12 or 12-7-6-4-4-6-7- 12. In addition, the GTP-binding domain of SEPT12 was crucial for its interaction with SEPT7, and the N- and C-termini of SEPT12 were required for the interaction of SEPT12 with itself to polymerize octamers into filaments. Mutant mice carrying the SEPT12D197N mutation, which disrupts SEPT12 filament formation, showed a disorganized sperm annulus, bent tail, reduced motility and loss of the SEPT ring structure at the sperm annulus. These phenotypes were also observed in an infertile man carrying SEPT12D197N. Taken together, our results demonstrate the molecular architecture of SEPT12 filaments at the sperm annulus, their mechanical support of sperm motility, and their correlation with male infertility.",
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SEPT12 orchestrates the formation of mammalian sperm annulus by organizing core octameric complexes with other SEPT proteins. / Kuo, Yung Che; Shen, Yi Ru; Chen, Hau Inh; Lin, Ying Hung; Wang, Ya Yun; Chen, Yet Ran; Wang, Chia-Yih; Kuo, Pao-Lin.

In: Journal of Cell Science, Vol. 128, No. 5, 01.01.2015, p. 923-934.

Research output: Contribution to journalArticle

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AU - Kuo, Yung Che

AU - Shen, Yi Ru

AU - Chen, Hau Inh

AU - Lin, Ying Hung

AU - Wang, Ya Yun

AU - Chen, Yet Ran

AU - Wang, Chia-Yih

AU - Kuo, Pao-Lin

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AB - Male infertility has become a worldwide health problem, but the etiologies of most cases are still unknown. SEPT12, a GTP-binding protein, is involved in male fertility. Two SEPT12 mutations (SEPT12T89M and SEPT12D197N) have been identified in infertile men who have a defective sperm annulus with a bent tail. The function of SEPT12 in the sperm annulus is still unclear. Here, we found that SEPT12 formed a filamentous structure with SEPT7, SEPT 6, SEPT2 and SEPT4 at the sperm annulus. The SEPT12- based septin core complex was assembled as octameric filaments comprising the SEPT proteins 12-7-6-2-2-6-7-12 or 12-7-6-4-4-6-7- 12. In addition, the GTP-binding domain of SEPT12 was crucial for its interaction with SEPT7, and the N- and C-termini of SEPT12 were required for the interaction of SEPT12 with itself to polymerize octamers into filaments. Mutant mice carrying the SEPT12D197N mutation, which disrupts SEPT12 filament formation, showed a disorganized sperm annulus, bent tail, reduced motility and loss of the SEPT ring structure at the sperm annulus. These phenotypes were also observed in an infertile man carrying SEPT12D197N. Taken together, our results demonstrate the molecular architecture of SEPT12 filaments at the sperm annulus, their mechanical support of sperm motility, and their correlation with male infertility.

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