Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 300, Taiwan.
Gynecologic Cancer Center, Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei 106, Taiwan.
Int J Mol Sci. 2018 Sep 5;19(9):2627. doi: 10.3390/ijms19092627.
() 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 in different codons resulted in teratozoospermia or oligozoospermia. In mouse models with a defective 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 caused defective sperm heads. This indicated that 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.
() 基因编码高度保守的聚合 GTP 结合细胞骨架蛋白。SEPT 的细胞功能包括有丝分裂、细胞骨架重塑、细胞极性和通过与各种类型的细胞骨架相互作用进行囊泡运输。我们发现不同密码子的突变 导致了畸形精子症或少精子症。在 缺陷的小鼠模型中，精子形态异常，精子数量减少，精子不动。然而，SEPT12 的调节因子完全未知。一些研究表明 CDC42 负调控哺乳动物细胞系中 SEPT2/6/7 复合物的聚合。在这项研究中，我们研究了 CDC42 是否调节 SEPT12 的聚合以及是否参与雄性生殖细胞的终末分化。首先，通过扫描电子显微镜分析，我们确定 的缺失导致精子头缺陷。这表明 对于精子头的形成至关重要。其次，CDC42 和 SEPT12 在伸长精子头部的围核区、伸长精子的颈部区和成熟精子的中段中具有相似的定位。第三，野生型 CDC42 和 CDC42Q61L（组成激活突变体）显著抑制 SEPT12 的聚合，但 CDC42T17N（显性失活突变体）没有，这通过异位表达分析得到证实。我们得出结论，CDC42 负调控 SEPT12 的聚合，并参与精子头的终末结构形成。
