Cation channel of sperm (CatSper)

The Cation channel of sperm (CatSper) is a sperm-specific, multi-subunit, voltage-gated calcium ion channel complex that is essential for the regulation of intracellular calcium influx in sperm tail, which enables hyperactivation, chemotaxis, and fertilization capacity of sperm. The channel is mainly composed of four distinct pore-forming alpha subunits (CATSPER1–4) and multiple auxiliary subunits (including CATSPERβ, γ, δ, ε, ζ, EFCAB9, and others), forming a supramolecular complex exclusively localized along specific domains of the sperm flagellum. CatSper is absolutely required for sperm hyperactivated motility and male fertility; disruption or genetic loss of any pore-forming subunit leads to male infertility, but does not affect other tissues. In humans, CatSper is polymodally activated by a variety of endogenous ligands, notably progesterone and prostaglandins, as well as some environmental chemicals and odorous compounds. Because of its sperm-specific expression and critical function, CatSper is a potential target for non-hormonal male contraception, but also presents safety challenges as any channel inhibitor can result in complete spermatogenic sterility. No therapeutic modulators are clinically approved; research compounds or environmental modulators remain the main means of CatSper manipulation.

Other names

CatSper channelCation/Calcium channel of spermSperm-specific calcium channelCATSPER1-4 (for the pore-forming subunits)CatSper complex

Allosteric activation/inhibition of channel opening (by steroids/prostaglandins or synthetic modulators); Direct agonism/antagonism at the channel pore or regulatory sites on subunits