SEPT12 phosphorylation results in loss of the septin ring/sperm annulus, defective sperm motility and poor male fertility

Yi Ru Shen, Han Yu Wang, Yung Che Kuo, Shih Chuan Shih, Chun Hua Hsu, Yet Ran Chen, Shang Rung Wu, Chia Yih Wang, Pao Lin Kuo

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Septins are critical for numerous cellular processes through the formation of heteromeric filaments and rings indicating the importance of structural regulators in septin assembly. Several posttranslational modifications (PTMs) mediate the dynamics of septin filaments in yeast. However, little is known about the role of PTMs in regulating mammalian septin assembly, and the in vivo significance of PTMs on mammalian septin assembly and function remains unknown. Here, we showed that SEPT12 was phosphorylated on Ser198 using mass spectrometry, and we generated SEPT12 phosphomimetic knock-in (KI) mice to study its biological significance. The homozygous KI mice displayed poor male fertility due to deformed sperm with defective motility and loss of annulus, a septin-based ring structure. Immunohistochemistry of KI testicular sections suggested that SEPT12 phosphorylation inhibits septin ring assembly during annulus biogenesis. We also observed that SEPT12 was phosphorylated via PKA, and its phosphorylation interfered with SEPT12 polymerization into complexes and filaments. Collectively, our data indicate that SEPT12 phosphorylation inhibits SEPT12 filament formation, leading to loss of the sperm annulus/septin ring and poor male fertility. Thus, we provide the first in vivo genetic evidence characterizing importance of septin phosphorylation in the assembly, cellular function and physiological significance of septins.

Original languageEnglish
Article numbere1006631
JournalPLoS genetics
Volume13
Issue number3
DOIs
Publication statusPublished - 2017 Mar

Fingerprint

Septins
Sperm Motility
male fertility
motility
sperm motility
sperm
Fertility
Spermatozoa
fertility
phosphorylation
post-translational modification
Phosphorylation
spermatozoa
polymerization
yeast
mass spectrometry
Post Translational Protein Processing
mice
immunohistochemistry
yeasts

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Shen, Yi Ru ; Wang, Han Yu ; Kuo, Yung Che ; Shih, Shih Chuan ; Hsu, Chun Hua ; Chen, Yet Ran ; Wu, Shang Rung ; Wang, Chia Yih ; Kuo, Pao Lin. / SEPT12 phosphorylation results in loss of the septin ring/sperm annulus, defective sperm motility and poor male fertility. In: PLoS genetics. 2017 ; Vol. 13, No. 3.
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SEPT12 phosphorylation results in loss of the septin ring/sperm annulus, defective sperm motility and poor male fertility. / Shen, Yi Ru; Wang, Han Yu; Kuo, Yung Che; Shih, Shih Chuan; Hsu, Chun Hua; Chen, Yet Ran; Wu, Shang Rung; Wang, Chia Yih; Kuo, Pao Lin.

In: PLoS genetics, Vol. 13, No. 3, e1006631, 03.2017.

Research output: Contribution to journalArticle

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AU - Shen, Yi Ru

AU - Wang, Han Yu

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AU - Hsu, Chun Hua

AU - Chen, Yet Ran

AU - Wu, Shang Rung

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