2. Academic Validation
  3. ACTN4 Mediates SEPT14 Mutation-Induced Sperm Head Defects

ACTN4 Mediates SEPT14 Mutation-Induced Sperm Head Defects

  • Biomedicines. 2020 Nov 19;8(11):518. doi: 10.3390/biomedicines8110518.
Yu-Hua Lin 1 2,  Chia-Yen Huang 3 4 5,  Chih-Chun Ke 6 7,  Ya-Yun Wang 8,  Tsung-Hsuan Lai 5 9,  Hsuan-Che Liu 8,  Wei-Chi Ku 5,  Chying-Chyuan Chan 10,  Ying-Hung Lin 8
Affiliations

Affiliations

  • 1 Department of Chemistry, Fu Jen Catholic University, New Taipei City 242, Taiwan.
  • 2 Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei City 231, Taiwan.
  • 3 Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 300, Taiwan.
  • 4 Gynecologic Cancer Center, Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei 106, Taiwan.
  • 5 School of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan.
  • 6 PhD Program in Nutrition & Food Science, Fu Jen Catholic University, New Taipei City 242, Taiwan.
  • 7 Department of Urology, En Chu Kong Hospital, New Taipei City 237, Taiwan.
  • 8 Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 242, Taiwan.
  • 9 Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei 106, Taiwan.
  • 10 Department of Obstetrics and Gynecology, Taipei City Hospital, Renai Branch, Taipei 106, Taiwan.
PMID: 33228246 DOI: 10.3390/biomedicines8110518
Abstract

Septins (SEPTs) are highly conserved GTP-binding proteins and the fourth component of the Cytoskeleton. Polymerized SEPTs participate in the modulation of various cellular processes, such as cytokinesis, cell polarity, and membrane dynamics, through their interactions with microtubules, actin, and other cellular components. The main objective of this study was to dissect the molecular pathological mechanism of SEPT14 mutation-induced sperm head defects. To identify SEPT14 interactors, co-immunoprecipitation (co-IP) and nano-liquid chromatography-mass spectrometry/mass spectrometry were applied. Immunostaining showed that SEPT14 was significantly localized to the manchette structure. The SEPT14 interactors were identified and classified as (1) SEPT-, (2) microtubule-, (3) actin-, and (4) sperm structure-related proteins. One interactor, ACTN4, an actin-holding protein, was selected for further study. Co-IP experiments showed that SEPT14 interacts with ACTN4 in a male germ cell line. SEPT14 also co-localized with ACTN4 in the perinuclear and manchette regions of the sperm head in early elongating spermatids. In the cell model, mutated SEPT14 disturbed the localization pattern of ACTN4. In a clinical aspect, sperm with mutant SEPT14, SEPT14A123T (p.Ala123Thr), and SEPT14I333T (p.Ile333Thr), have mislocalized and fragmented ACTN4 signals. Sperm head defects in donors with SEPT14 mutations are caused by disruption of the functions of ACTN4 and actin during sperm head formation.

Keywords

ACTN4; SEPT14; male infertility; septin; teratozoospermia.

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