Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav-IPN), Departamento de Biología Celular, Ciudad de México 07360, Mexico.
Instituto Mexicano del Seguro Social (IMSS), Hospital General de Zona Núm. 68, Ecatepec 55400, Mexico.
Int J Mol Sci. 2022 Jul 22;23(15):8070. doi: 10.3390/ijms23158070.
The CatSper channel localizes exclusively in the flagella of sperm cells. The Catsper1 protein, together with three pore units, is essential for the CatSper Channel formation, which produces flagellum hyperactivation and confers sperm fertility. expression is dependent on Sox transcription factors, which can recognize in vitro at least three Sox binding sites on the promoter. Sox transcription factors have calmodulin-binding domains for nuclear importation. Calmodulin (CaM) is affected by the specific inhibitor calmidazolium (CMZ), which prevents the nuclear transport of Sox factors. In this work, we assess the regulation of the promoter in vivo by Sox factors in the murine testis and evaluate the effects of the inhibitor calmidazolium on the expression of the genes, and the motility and fertility of the sperm. promoter has significant transcriptional activity in vivo; on the contrary, three Sox site mutants in the promoter reduced transcriptional activity in the testis. CaM inhibition affects Sox factor nuclear transport and has notable implications in the expression and production of , as well as in the motility and fertility capability of sperm. The molecular mechanism described here might conform to the basis of a male contraceptive strategy acting at the transcriptional level by affecting the production of the CatSper channel, a fundamental piece of male fertility.
CatSper 通道仅定位于精子的鞭毛中。Catsper1 蛋白与三个 pore 单位一起对于 CatSper 通道的形成是必不可少的，该通道产生鞭毛过度激活并赋予精子活力。表达依赖于 Sox 转录因子，该因子可以在体外至少识别启动子上的三个 Sox 结合位点。Sox 转录因子具有钙调蛋白结合结构域以进行核输入。钙调蛋白 (CaM) 受特定抑制剂氯氮䓬 (CMZ) 的影响，该抑制剂阻止 Sox 因子的核转运。在这项工作中，我们评估了 Sox 因子在体内对小鼠睾丸中 启动子的调节，并评估了抑制剂氯氮䓬对 基因表达、精子运动性和活力的影响。发现 启动子在体内具有显著的转录活性；相反， 启动子中的三个 Sox 位点突变体降低了睾丸中的转录活性。CaM 抑制影响 Sox 因子的核转运，并对 表达和产生以及精子的运动性和活力能力产生显著影响。此处描述的分子机制可能构成了一种男性避孕药具策略的基础，该策略通过影响 CatSper 通道的产生而在转录水平上发挥作用，CatSper 通道是男性生育力的重要组成部分。
