Cation channel sperm-associated protein 1 (CatSper1) (CatSper1)

Cation channel sperm-associated protein 1 (CatSper1) is a vital pore-forming subunit of the CatSper channel, a sperm-specific, pH-dependent calcium channel located in the flagellum (UniProt Q8NEC5). It is essential for sperm hyperactivation, a high-amplitude, asymmetrical beating pattern required for sperm to penetrate the egg's zona pellucida during fertilization (Ren et al., 2001, PMID: 11595941). Because its expression is restricted to the testis and mature sperm, CatSper1 is a premier target for non-hormonal male contraception, offering a path to prevent pregnancy without affecting systemic endocrine balance (Lishko & Mannowetz, 2018, PMID: 28539441). Mutations in the CATSPER1 gene are associated with male infertility and asthenozoospermia in humans (Avenarius et al., 2009, PMID: 19384953). Pharmacological inhibition of CatSper1 using compounds like HC-056456 or NNC 55-0396 has been shown to block calcium signaling and prevent fertilization in animal models (Carlson et al., 2009, PMID: 19233911). Despite its potential, challenges remain in achieving high potency and selectivity over other ion channels to ensure safety and reversibility in clinical applications. Current research is focused on identifying small molecules that can be administered on-demand to provide rapid-onset contraception. The channel's unique structure, involving four different alpha-like subunits (CatSper1-4), provides multiple sites for potential drug interaction.

Other names

CATSPER1Cation channel sperm-associated protein 1Sperm-associated cation channel 1CATSPER

Inhibition of the CatSper1-containing channel complex prevents the alkaline-induced calcium influx into the sperm flagellum, thereby blocking the transition to hyperactivated motility required for fertilization (Lishko & Mannowetz, 2018, PMID: 28539441).