The CatSper channel: a polymodal chemosensor in human sperm
The CatSper channel: a polymodal chemosensor in human sperm
复制标题
DOI：
10.1038/emboj.2012.30
复制
发表时间：
2012-04-04
期刊：
影响因子：
11.4
通讯作者：
Struenker, Timo
中科院分区：
文献类型：
--
作者：
Brenker, Christoph;Goodwin, Normann;Struenker, Timo
精子特异的CatSper通道控制细胞内钙离子浓度([Ca~(2+)](I))，从而控制精子的游泳行为。在人类中，CatSper直接被孕酮和前列腺素激活--这是刺激钙离子内流的女性因素。其他因素包括神经递质、趋化因子和气味也通过改变[钙]i来影响精子功能。一些配体，特别是气味，已被提出通过G蛋白偶联受体(GPCRs)和cAMP信号通路来控制钙进入和运动。在这里，我们展示了气味直接激活CatSper，而不涉及GPCRs和cAMP。此外，经常被用于研究cAMP介导的钙信号转导的环核苷酸的膜通透性类似物也通过细胞外位点直接激活CatSper。因此，CatSper或相关蛋白(S)含有可以容纳各种配体的混杂结合位点。这些结果挑战了目前关于哺乳动物精子中通过GPCR和cAMP传递钙信号的概念：被认为激活新陈代谢途径的配体实际上是通过共同的离子亲和机制发挥作用的。我们认为CatSper通道复合体是一种多模式传感器，可以检测多种化学信号，帮助精子在穿越女性生殖道的过程中发挥作用。《EMBO期刊》(2012)31,1654-1665。DOI：10.1038/Intemj.2012.30；2012年2月21日在线发布
The sperm-specific CatSper channel controls the intracellular Ca2+ concentration ([Ca2+](i)) and, thereby, the swimming behaviour of sperm. In humans, CatSper is directly activated by progesterone and prostaglandins-female factors that stimulate Ca2+ influx. Other factors including neurotransmitters, chemokines, and odorants also affect sperm function by changing [Ca2+]i. Several ligands, notably odorants, have been proposed to control Ca2+ entry and motility via G protein-coupled receptors (GPCRs) and cAMP-signalling pathways. Here, we show that odorants directly activate CatSper without involving GPCRs and cAMP. Moreover, membrane-permeable analogues of cyclic nucleotides that have been frequently used to study cAMP-mediated Ca2+ signalling also activate CatSper directly via an extracellular site. Thus, CatSper or associated protein(s) harbour promiscuous binding sites that can host various ligands. These results contest current concepts of Ca2+ signalling by GPCR and cAMP in mammalian sperm: ligands thought to activate metabotropic pathways, in fact, act via a common ionotropic mechanism. We propose that the CatSper channel complex serves as a polymodal sensor for multiple chemical cues that assist sperm during their voyage across the female genital tract. The EMBO Journal (2012) 31, 1654-1665. doi: 10.1038/emboj.2012.30; Published online 21 February 2012