Lishko Polina V, Mannowetz Nadja
Curr Opin Physiol. 2018 Apr;2:109-113. doi: 10.1016/j.cophys.2018.02.004. Epub 2018 Feb 22.
To overcome egg protective vestments and ensure successful fertilization, mammalian spermatozoa switch symmetrical progressive motility to a powerful, whip-like flagellar motion, known as hyperactivation. The latter is triggered by a calcium influx through the sperm-specific, voltage-dependent, and alkalization-activated calcium channel of sperm - CatSper. The channel comprises nine subunits which together form a heteromeric complex. CatSper-deficient male mice and men with mutations in CatSper genes are infertile. This calcium channel is regulated by various endogenous compounds, such as steroids, prostaglandins, endocannabinoids, and intracellular pH. Being a sperm-specific ion channel that is not expressed anywhere else in the body, CatSper represents an ideal target for the development of female and even male contraceptives. In this review, we discuss the recent advances in studying CatSper functional properties and discuss future steps that are required to take in order to achieve a deep understanding of the molecular basis of CatSper function.
为了克服卵子的保护屏障并确保受精成功,哺乳动物的精子会将对称的渐进性运动转变为有力的、类似鞭子的鞭毛运动,即超活化。后者由钙离子通过精子特异性、电压依赖性且碱化激活的精子钙通道(CatSper)内流触发。该通道由九个亚基组成,共同形成一个异源复合体。CatSper基因缺陷的雄性小鼠以及CatSper基因突变的男性均不育。这种钙通道受多种内源性化合物调节,如类固醇、前列腺素、内源性大麻素和细胞内pH值。作为一种在体内其他任何地方都不表达的精子特异性离子通道,CatSper是开发女性甚至男性避孕药的理想靶点。在本综述中,我们讨论了研究CatSper功能特性的最新进展,并探讨了为深入理解CatSper功能的分子基础而需要采取的未来步骤。