1.A.1.19.1
Alkalinizatioin-activated Ca²⁺-selective channel, sperm-associated cation channel, CatSper, required for male fertility and the hyperactivated motility of spermatozoa (Kirichok et al. 2006). These channels require auxiliary subunits, CatSperβ, γ and δ for activity (Chung et al., 2011).  The primary channel protein is CatSper1 (Liu et al., 2007), and it may be a target for immunocontraception (Li et al. 2009). CatSper channels have been reported to regulate sperm motility (Vicente-Carrillo et al. 2017). Sperm competition is selective for a disulfide-crosslinked macromolecular architecture. CatSper channel opening occurs in response to pH, 2-arachidonoylglycerol, and mechanical force. A flippase function is hypothesized, and a source of the concomitant disulfide isomerase activity is found in CatSper-associated proteins beta, delta and epsilon (Bystroff 2018). More recently, it has been reported that rotational motion and rheotaxis of human sperm do not require functional CatSper channels or transmembrane Ca²⁺ signaling (Schiffer et al. 2020). Instead, passive biomechanical and hydrodynamic processes may enable sperm rolling and rheotaxis, rather than calcium signaling mediated by CatSper or other mechanisms controlling transmembrane Ca²⁺ flux. The Ca²⁺ channel CatSper is not activated by cAMP/PKA signaling but directly affected by chemicals used to probe the action of cAMP and PKA (Wang et al. 2020). The cation channel of sperm (CatSper) is essential for sperm motility and fertility. CatSper comprises the pore-forming proteins CATSPER1-4 and multiple auxiliary subunits, including CATSPERbeta, gamma, delta, epsilon, zeta, and EFCAB9. Lin et al. 2021 reported the cryo-EM structure of the CatSper complex isolated from mouse sperm. CATSPER1-4 conform to the conventional domain-swapped voltage-gated ion channel fold, following a counterclockwise arrangement. The auxiliary subunits CATSPERbeta, gamma, delta and epsilon - each of which contains a single transmembrane segment and a large extracellular domain - constitute a pavilion-like structure that stabilizes the entire complex through interactions with CATSPER4, 1, 3 and 2, respectively. The EM map revealed several previously uncharacterized components, exemplified by the organic anion transporter SLCO6C1. Lin et al. 2021 named this channel-transporter ultracomplex the CatSpermasome. The assembly and organizational details of the CatSpermasome lay the foundation for the development of CatSpermasome-related treatments for male infertility and non-hormonal contraceptives. CatSper is a target for inhibition, for use in male contraception, causing inhibition of sperm motility (Mariani et al. 2023).