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EMBO J. 2012 Apr 4;31(7):1654-65. doi: 10.1038/emboj.2012.30. Epub 2012 Feb 21.

The CatSper channel: a polymodal chemosensor in human sperm.

Author information

1
Center of Advanced European Studies and Research (caesar), Abteilung Molekulare Neurosensorik, Bonn, Germany.

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.

PMID:
22354039
PMCID:
PMC3321208
DOI:
10.1038/emboj.2012.30
[Indexed for MEDLINE]
Free PMC Article

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