The cation channels of sperm also known as Catsper channels or CatSper, are
ion channel
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...
s that are related to the
two-pore channels and distantly related to
TRP channels. The four members of this family form
voltage-gated Ca
2+ channels that seem to be specific to sperm. As sperm encounter the more alkaline environment of the female reproductive tract, CatSper channels become activated by the altered ion concentration. These channels are required for proper fertilization.
The study of these channels has been slow because they do not traffic to the
cell membrane in many
heterologous systems.
There are several factors that can activate the CatSper calcium channel, depending on species. In the human, the channel is activated by
progesterone
Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...
released by the
oocyte. Progesterone binds to the protein
ABHD2 which is present in the sperm plasma membrane, which causes ABHD2 to cleave an inhibitor of CatSper (
2-arachidonoylglycerol
2-Arachidonoylglycerol (2-AG) is an endocannabinoid, an endogenous agonist of the CB1 receptor and the primary endogenous ligand for the CB2 receptor. It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol. It is present ...
) into
arachidonic acid
Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''arachi ...
and
glycerol. The human CatSper channel is pH-sensitive, and requires a high-pH environment. CatSper plays a key role in mediating hyperactive motility – prior to fertilization, sperm become entrapped within the fingerlike projections of the
microvilli
Microvilli (singular: microvillus) are microscopic cellular membrane protrusions that increase the surface area for diffusion and minimize any increase in volume, and are involved in a wide variety of functions, including absorption, secretion, ...
of the oviduct. In order for the sperm to fertilize the oocyte, CatSper must be present in order to initiate hyperactive motility, allowing the sperm to escape the microvilli and reach the oocyte for fertilization.
Certain substances act as agonist or inhibitor of CatSper (e. g.
Pregnenolone sulfate is an agonist,
pristimerin and
lupeol are inhibitors).
Of the four members of the Catsper family, Catsper1 is found in the primary piece of sperm. Catsper1 plays an important role in evoked Ca
2+ entry and regulation of
hyperactivation
Hyperactivation is a type of sperm motility. Hyperactivated sperm motility is characterised by a high amplitude, asymmetrical beating pattern of the sperm tail ( flagellum). This type of motility may aid in sperm penetration of the zona pelluc ...
in sperm. Catsper2 is localized in the sperm tail and is responsible for regulation of hyperactivation. Catsper3 and Catsper4 are found in both, the testes and sperm and play an important role in the motility of hyperactivated sperm. In humans, CatSper is distributed in quadrilateral nanodomains along the principal piece. Although Catsper seems to play an important role in sperm function, Catspers1-4 null mice have been found to have normal testicular histology, sperm counts and morphology, which is indicative of normal progression of
spermatogenesis
Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testis. This process starts with the mitotic division of the stem cells located close to the basement membrane of the tubule ...
.
See also
*
Acrosome reaction
References
External links
*
GeneReviews/NCBI/NIH/UW entry on CATSPER-Related Male Infertility*
{{Ion channels, g1
Ion channels
Voltage-gated ion channels
Transmembrane proteins
Electrophysiology
Calcium channels