| Title: | The CatSper channel: a polymodal chemosensor in human sperm |
| Author(s): | Brenker C; Goodwin N; Weyand I; Kashikar ND; Naruse M; Krahling M; Muller A; Kaupp UB; Strunker T; |
| Address: | "Center of Advanced European Studies and Research (caesar), Abteilung Molekulare Neurosensorik, Bonn, Germany" |
| ISSN/ISBN: | 1460-2075 (Electronic) 0261-4189 (Print) 0261-4189 (Linking) |
| Abstract: | "The sperm-specific CatSper channel controls the intracellular Ca(2+) concentration ([Ca(2+)](i)) and, thereby, the swimming behaviour of sperm. In humans, CatSper is directly activated by progesterone and prostaglandins-female factors that stimulate Ca(2+) influx. Other factors including neurotransmitters, chemokines, and odorants also affect sperm function by changing [Ca(2+)](i). Several ligands, notably odorants, have been proposed to control Ca(2+) 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 Ca(2+) 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 Ca(2+) 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" |
| Keywords: | Aldehydes/pharmacology Benzimidazoles/pharmacology Calcium Channel Blockers/pharmacology Calcium Channels/*metabolism Calcium Signaling/drug effects/*physiology Cyclic AMP/metabolism Cyclopropanes/pharmacology Humans Male Mibefradil/pharmacology Naphthale; |
| Notes: | "MedlineBrenker, Christoph Goodwin, Normann Weyand, Ingo Kashikar, Nachiket D Naruse, Masahiro Krahling, Miriam Muller, Astrid Kaupp, U Benjamin Strunker, Timo eng Research Support, Non-U.S. Gov't England 2012/02/23 EMBO J. 2012 Apr 4; 31(7):1654-65. doi: 10.1038/emboj.2012.30. Epub 2012 Feb 21" |
