CCR6 is required for ligand-induced CatSper activation in human sperm.

CatSper channel has been considered the principal sperm Ca2+ channel responsible for the cytosolic Ca2+ elevation required for various sperm functions necessary for fertilization. However, the mechanism underlying the activation of CatSper channel by various physiological ligands remain incompletely understood. We have recently demonstrated the expression of C-C chemokine receptor 6 (CCR6) in sperm and Ca2+ influx upon binding of human β-defensin 1 (DEFB1) to CCR6, which is important for sperm motility. In the present study, we have demonstrated that CCR6 receptor and CatSper channel are both required for the Ca2+ entry/current induced by physiological ligands DEFB1, chemokine (C-C motif) ligand 20 (CCL20) and progesterone in human sperm. CCR6 is co-localized and interacts with CatSper in human sperm. Ca2+ influx mediated by CCR6 and CatSper is required for essential sperm functions, including motility, hyperactivation and acrosome reaction, which are impaired in infertile sperm showing reduced levels of CCR6 and CatSper. The present finding suggests a critical role of CCR6 receptor in mediating ligand-induced, CatSper-dependent Ca2+ influx required for various sperm functions and thus male fertility.

CatSper通道被认为是主要的精子钙离子通道，负责受精所必需的各种精子功能所需的胞质钙离子浓度升高。然而，各种生理配体激活CatSper通道的潜在机制仍未完全清楚。我们最近证实了C - C趋化因子受体6（CCR6）在精子中的表达，以及人β - 防御素1（DEFB1）与CCR6结合时的钙离子内流，这对精子活力很重要。在本研究中，我们已经证明，对于生理配体DEFB1、趋化因子（C - C基序）配体20（CCL20）和孕酮在人精子中诱导的钙离子进入/电流，CCR6受体和CatSper通道都是必需的。在人精子中，CCR6与CatSper共定位并相互作用。由CCR6和CatSper介导的钙离子内流是精子基本功能所必需的，包括活力、超激活和顶体反应，在不育精子中这些功能受损，同时CCR6和CatSper水平降低。目前的研究结果表明，CCR6受体在介导配体诱导的、CatSper依赖的钙离子内流中起着关键作用，这种钙离子内流是各种精子功能以及男性生育能力所必需的。