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SEPT12-Microtubule Complexes Are Required for Sperm Head and Tail Formation
Department of Obstetrics & Gynaecology, National Cheng Kung University, No. 1, University Road, Tainan City 701, Taiwan
Graduate Institute of Basic Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Road, Xinzhuang District, New Taipei City 242, Taiwan
Graduate Institute of Basic Medical Sciences, National Cheng Kung University, No. 1, University Road, Tainan City 701, Taiwan
Research Center for Emerging Viral Infections, Chang Gung University, No. 259 Wen-Hwa 1st Road, Kwei-Shan Taoyuan 333, Taiwan
Laboratory Animal Center, National Taiwan University College of Medicine, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan
Department of Biological Sciences and Technology, National University of Tainan, No. 33, Sec. 2, Shulin Street, West Central District, Tainan City 700, Taiwan
Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, National Taiwan University Hospital, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 6 September 2013; in revised form: 26 September 2013 / Accepted: 26 September 2013 / Published: 7 November 2013
Abstract: The septin gene belongs to a highly conserved family of polymerizing GTP-binding cytoskeletal proteins. SEPTs perform cytoskeletal remodeling, cell polarity, mitosis, and vesicle trafficking by interacting with various cytoskeletons. Our previous studies have indicated that SEPTIN12+/+/+/− chimeras with a SEPTIN12 mutant allele were infertile. Spermatozoa from the vas deferens of chimeric mice indicated an abnormal sperm morphology, decreased sperm count, and immotile sperm. Mutations and genetic variants of SEPTIN12 in infertility cases also caused oligozoospermia and teratozoospermia. We suggest that a loss of SEPT12 affects the biological function of microtublin functions and causes spermiogenesis defects. In the cell model, SEPT12 interacts with α- and β-tubulins by co-immunoprecipitation (co-IP). To determine the precise localization and interactions between SEPT12 and α- and β-tubulins in vivo, we created SEPTIN12-transgene mice. We demonstrate how SEPT12 interacts and co-localizes with α- and β-tubulins during spermiogenesis in these mice. By using shRNA, the loss of SEPT12 transcripts disrupts α- and β-tubulin organization. In addition, losing or decreasing SEPT12 disturbs the morphogenesis of sperm heads and the elongation of sperm tails, the steps of which are coordinated and constructed by α- and β-tubulins, in SEPTIN12+/+/+/− chimeras. In this study, we discovered that the SEPTIN12-microtubule complexes are critical for sperm formation during spermiogenesis.
Keywords: spermiogenesis; SEPT12; microtubules
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Kuo, P.-L.; Chiang, H.-S.; Wang, Y.-Y.; Kuo, Y.-C.; Chen, M.-F.; Yu, I.-S.; Teng, Y.-N.; Lin, S.-W.; Lin, Y.-H. SEPT12-Microtubule Complexes Are Required for Sperm Head and Tail Formation. Int. J. Mol. Sci. 2013, 14, 22102-22116.
Kuo P-L, Chiang H-S, Wang Y-Y, Kuo Y-C, Chen M-F, Yu I-S, Teng Y-N, Lin S-W, Lin Y-H. SEPT12-Microtubule Complexes Are Required for Sperm Head and Tail Formation. International Journal of Molecular Sciences. 2013; 14(11):22102-22116.
Kuo, Pao-Lin; Chiang, Han-Sun; Wang, Ya-Yun; Kuo, Yung-Che; Chen, Mei-Feng; Yu, I-Shing; Teng, Yen-Ni; Lin, Shu-Wha; Lin, Ying-Hung. 2013. "SEPT12-Microtubule Complexes Are Required for Sperm Head and Tail Formation." Int. J. Mol. Sci. 14, no. 11: 22102-22116.