RT Journal Article
SR Electronic
T1 OR1D2 receptor mediates bourgeonal-induced human CatSper activation in a G-protein dependent manner
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 757880
DO 10.1101/757880
A1 Yi-min Cheng
A1 Tao Luo
A1 Zhen Peng
A1 Hou-yang Chen
A1 Jin Zhang
A1 Xu-Hui Zeng
YR 2019
UL http://biorxiv.org/content/early/2019/09/06/757880.abstract
AB During fertilization, sperm are guided towards eggs by physiological chemokines, a process named sperm chemotaxis. Human sperm chemotaxis is speculated to be mediated by olfactory receptor OR1D2 in a pathway requiring calcium influx. Bourgeonal, an artificial ligand of OR1D2, can activate CatSper, the primary calcium channel in human sperm. However, whether bourgeonal-induced CatSper activation requires OR1D2 and how CatSper is activated remain unclear. Herein, we show that OR1D2 antibody can inhibit bourgeonal-induced CatSper activation and sperm chemotaxis, proving that OR1D2 mediates bourgeonal-induced CatSper activation. Furthermore, bourgeonal-evoked CatSper currents can be greatly suppressed by either GDP-β-S or antibody of Gαs. Interestingly, bourgeonal can transiently increase sperm cAMP level, and this effect can be abolished by OR1D2 antibody. Consistently, bourgeonal-induced CatSper activation can be inhibited by membrane adenylate cyclases inhibitor. Overall, our results indicate that bourgeonal activates CatSper via OR1D2-G protein-cAMP pathway. Although CatSper can be activated by various physiological and environmental factors, this study represents the most recent progress proving that CatSper can be indirectly activated by extracellular regulators through a G-protein-dependent intracellular signaling pathway.