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CDC42 Negatively Regulates Testis-Specific SEPT12 Polymerization.
Huang, Chia-Yen; Wang, Ya-Yun; Chen, Ying-Liang; Chen, Mei-Feng; Chiang, Han-Sun; Kuo, Pao-Lin; Lin, Ying-Hung.
Afiliação
  • Huang CY; Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 300, Taiwan. bagiao2003@gmail.com.
  • Wang YY; Gynecologic Cancer Center, Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei 106, Taiwan. bagiao2003@gmail.com.
  • Chen YL; School of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan. bagiao2003@gmail.com.
  • Chen MF; Department of Chemistry, Fu Jen Catholic University, New Taipei City 242, Taiwan. vic0009@gmail.com.
  • Chiang HS; Department of Environmental Engineering, National Cheng Kung University, Tainan 701, Taiwan. roy.yl.chen@gmail.com.
  • Kuo PL; Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan. mfchen0@gmail.com.
  • Lin YH; Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 242, Taiwan. 053824@mail.fju.edu.tw.
Int J Mol Sci ; 19(9)2018 Sep 05.
Article em En | MEDLINE | ID: mdl-30189608
Septin (SEPT) genes encode well-preserved polymerizing GTP-binding cytoskeletal proteins. The cellular functions of SEPTs consist of mitosis, cytoskeletal remodeling, cell polarity, and vesicle trafficking through interactions with various types of cytoskeletons. We discovered that mutated SEPTIN12 in different codons resulted in teratozoospermia or oligozoospermia. In mouse models with a defective Septin12 allele, sperm morphology was abnormal, sperm count decreased, and sperms were immotile. However, the regulators of SEPT12 are completely unknown. Some studies have indicated that CDC42 negatively regulates the polymerization of SEPT2/6/7 complexes in mammalian cell lines. In this study, we investigated whether CDC42 modulates SEPT12 polymerization and is involved in the terminal differentiation of male germ cells. First, through scanning electron microscopy analysis, we determined that the loss of Septin12 caused defective sperm heads. This indicated that Septin12 is critical for the formation of sperm heads. Second, CDC42 and SEPT12 were similarly localized in the perinuclear regions of the manchette at the head of elongating spermatids, neck region of elongated spermatids, and midpiece of mature spermatozoa. Third, wild-type CDC42 and CDC42Q61L (a constitutive-acting-mutant) substantially repressed SEPT12 polymerization, but CDC42T17N (a dominant-negative-acting mutant) did not, as evident through ectopic expression analysis. We concluded that CDC42 negatively regulates SEPT12 polymerization and is involved in terminal structure formation of sperm heads.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Testículo / Regulação da Expressão Gênica / Proteína cdc42 de Ligação ao GTP / Multimerização Proteica / Septinas Limite: Animals / Humans / Male Idioma: En Revista: Int J Mol Sci Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Taiwan

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Testículo / Regulação da Expressão Gênica / Proteína cdc42 de Ligação ao GTP / Multimerização Proteica / Septinas Limite: Animals / Humans / Male Idioma: En Revista: Int J Mol Sci Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Taiwan