title: SEPT12-microtubule complexes are required for sperm head and tail formation.
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.
authors.affiliation: Department of Obstetrics & Gynaecology, National Cheng Kung University, No. 1, University Road, Tainan City 701, Taiwan. 084952@mail.fju.edu.tw.
authors.forename: Pao-Lin
authors.initials: PL
authors.lastname: Kuo
authors.forename: Han-Sun
authors.initials: HS
authors.lastname: Chiang
authors.forename: Ya-Yun
authors.initials: YY
authors.lastname: Wang
authors.forename: Yung-Che
authors.initials: YC
authors.lastname: Kuo
authors.forename: Mei-Feng
authors.initials: MF
authors.lastname: Chen
authors.forename: I-Shing
authors.initials: IS
authors.lastname: Yu
authors.forename: Yen-Ni
authors.initials: YN
authors.lastname: Teng
authors.forename: Shu-Wha
authors.initials: SW
authors.lastname: Lin
authors.forename: Ying-Hung
authors.initials: YH
authors.lastname: Lin
mesh_terms: D000818:Animals; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism*; D058112:Septins / Q000737:chemistry / Q000378:metabolism*; D013077:Sperm Head / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D013082:Sperm Tail / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D013091:Spermatogenesis; D013094:Spermatozoa / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; C502729:SEPTIN12 protein, human; D058112:Septins