title: The CatSper channel: a polymodal chemosensor in human sperm.
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.
authors.affiliation: Center of Advanced European Studies and Research (caesar), Abteilung Molekulare Neurosensorik, Bonn, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Brenker
authors.forename: Normann
authors.initials: N
authors.lastname: Goodwin
authors.forename: Ingo
authors.initials: I
authors.lastname: Weyand
authors.forename: Nachiket D
authors.initials: ND
authors.lastname: Kashikar
authors.forename: Masahiro
authors.initials: M
authors.lastname: Naruse
authors.forename: Miriam
authors.initials: M
authors.lastname: Krähling
authors.forename: Astrid
authors.initials: A
authors.lastname: Müller
authors.forename: U Benjamin
authors.initials: UB
authors.lastname: Kaupp
authors.forename: Timo
authors.initials: T
authors.lastname: Strünker
mesh_terms: D000447:Aldehydes / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D003521:Cyclopropanes / Q000494:pharmacology; D006801:Humans; D008297:Male; D020748:Mibefradil / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010675:Pheromones / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000447:Aldehydes; D001562:Benzimidazoles; C438823:CATSPER1 protein, human; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D003521:Cyclopropanes; D009281:Naphthalenes; D010675:Pheromones; D043562:Receptors, G-Protein-Coupled; C484287:NNC 55-0396; D020748:Mibefradil; C479548:undecanal; D000242:Cyclic AMP; C473193:bourgeonal