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 (electrophysiol ...

s that are related to the two-pore channels and distantly related to TRP channels. The four members of this family form voltage-gated Ca²⁺ 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 The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

in many

heterologous The term heterologous has several meanings in biology. Gene expression In cell biology and protein biochemistry, heterologous expression means that a protein is experimentally put into a cell that does not normally make (i.e., express) that ...

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 ma ...

released by the

oocyte An oocyte (, oöcyte, or ovocyte) is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ger ...

. Progesterone binds to the protein

ABHD2 Abhydrolase domain-containing protein 2 is a serine hydrolase enzyme that is strongly expressed in human spermatozoa. It is a key controller of sperm hyperactivation, which is a necessary step in allowing sperm to fertilize an egg. It is encode ...

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 pres ...

) 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 a precursor in the formation of leukotrienes, prostaglandins, and thromboxanes. Together with omega−3 fatty acids an ...

and

glycerol Glycerol () is a simple triol compound. It is a colorless, odorless, sweet-tasting, viscous liquid. The glycerol backbone is found in lipids known as glycerides. It is also widely used as a sweetener in the food industry and as a humectant in pha ...

. 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 (: 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, cellula ...

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 Lupeol is a pharmacologically active pentacyclic triterpenoid. It has several potential medicinal properties, like anticancer and anti-inflammatory activity. Natural occurrences Lupeol is found in a variety of plants, including mango, '' Acaci ...

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 Ca²⁺ entry and regulation of hyperactivation 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 testicle. This process starts with the Mitosis, mitotic division of the stem cells located close to the basement membrane of ...

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

See also

References

External links