標題: CDC42 Negatively Regulates Testis-Specific SEPT12 Polymerization
作者: Huang, Chia-Yen
Wang, Ya-Yun
Chen, Ying-Liang
Chen, Mei-Feng
Chiang, Han-Sun
Kuo, Pao-Lin
Lin, Ying-Hung
生物科技學系
Department of Biological Science and Technology
關鍵字: SEPT;SEPT12;CDC42;sperm
公開日期: 1-Sep-2018
摘要: 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.
URI: http://dx.doi.org/10.3390/ijms19092627
http://hdl.handle.net/11536/148455
ISSN: 1422-0067
DOI: 10.3390/ijms19092627
期刊: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume: 19
Appears in Collections:Articles