Cation channels of sperm | |||||||||
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Identifiers | |||||||||
Symbol | CATSPER | ||||||||
Pfam | PF15020 | ||||||||
InterPro | IPR028246 | ||||||||
Membranome | 222 | ||||||||
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cation channel, sperm associated 1 | |||||||
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Identifiers | |||||||
Symbol | CATSPER1 | ||||||
IUPHAR | 388 | ||||||
NCBI gene | 117144 | ||||||
HGNC | 17116 | ||||||
OMIM | 606389 | ||||||
RefSeq | NM_053054 | ||||||
UniProt | Q8NEC5 | ||||||
Other data | |||||||
Locus | Chr. 11 q12.1 | ||||||
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cation channel, sperm associated 2 | |||||||
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Identifiers | |||||||
Symbol | CATSPER2 | ||||||
IUPHAR | 389 | ||||||
NCBI gene | 117155 | ||||||
HGNC | 18810 | ||||||
OMIM | 607249 | ||||||
RefSeq | NM_172097 | ||||||
UniProt | Q96P55 | ||||||
Other data | |||||||
Locus | Chr. 15 q13-q15 | ||||||
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cation channel, sperm associated 3 | |||||||
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Identifiers | |||||||
Symbol | CATSPER3 | ||||||
IUPHAR | 390 | ||||||
NCBI gene | 347732 | ||||||
HGNC | 20819 | ||||||
OMIM | 609120 | ||||||
RefSeq | NM_178019 | ||||||
UniProt | Q86XQ3 | ||||||
Other data | |||||||
Locus | Chr. 5 q31.2 | ||||||
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cation channel, sperm associated 4 | |||||||
---|---|---|---|---|---|---|---|
Identifiers | |||||||
Symbol | CATSPER4 | ||||||
IUPHAR | 391 | ||||||
NCBI gene | 378807 | ||||||
HGNC | 23220 | ||||||
OMIM | 609121 | ||||||
RefSeq | NM_198137 | ||||||
UniProt | Q7RTX7 | ||||||
Other data | |||||||
Locus | Chr. 1 p35.3 | ||||||
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The cation channels of sperm also known as Catsper channels or CatSper, are ion channels 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. [1] The study of these channels has been slow because they do not traffic to the cell membrane in many heterologous systems. [2]
There are several factors that can activate the CatSper calcium channel, depending on species. In the human, the channel is activated by progesterone released by the oocyte. [3] 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) into arachidonic acid and glycerol. [4] The human CatSper channel is pH-sensitive, and requires a high-pH environment. [5] CatSper plays a key role in mediating hyperactive motility – prior to fertilization, sperm become entrapped within the fingerlike projections of the microvilli 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. [6]
Certain substances act as agonist or inhibitor of CatSper (e. g. Pregnenolone sulfate is an agonist, pristimerin and lupeol are inhibitors). [7]
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. [8] 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. [9]
A spermatozoon is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote.
During fertilization, a sperm must first fuse with the plasma membrane and then penetrate the female egg cell to fertilize it. Fusing to the egg cell usually causes little problem, whereas penetrating through the egg's hard shell or extracellular matrix can be more difficult. Therefore, sperm cells go through a process known as the acrosome reaction, which is the reaction that occurs in the acrosome of the sperm as it approaches the egg.
Steroid hormone receptors are found in the nucleus, cytosol, and also on the plasma membrane of target cells. They are generally intracellular receptors and initiate signal transduction for steroid hormones which lead to changes in gene expression over a time period of hours to days. The best studied steroid hormone receptors are members of the nuclear receptor subfamily 3 (NR3) that include receptors for estrogen and 3-ketosteroids. In addition to nuclear receptors, several G protein-coupled receptors and ion channels act as cell surface receptors for certain steroid hormones.
Capacitation is the penultimate step in the maturation of mammalian spermatozoa and is required to render them competent to fertilize an oocyte. This step is a biochemical event; the sperm move normally and look mature prior to capacitation. In vivo, capacitation occurs after ejaculation, when the spermatozoa leave the vagina and enter the upper female reproductive tract. The uterus aids in the steps of capacitation by secreting sterol-binding albumin, lipoproteins, and proteolytic and glycosidasic enzymes such as heparin.
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 pellucida, which encloses the ovum.
Cyclic nucleotide–gated ion channels or CNG channels are ion channels that function in response to the binding of cyclic nucleotides. CNG channels are nonselective cation channels that are found in the membranes of various tissue and cell types, and are significant in sensory transduction as well as cellular development. Their function can be the result of a combination of the binding of cyclic nucleotides and either a depolarization or a hyperpolarization event. Initially discovered in the cells that make up the retina of the eye, CNG channels have been found in many different cell types across both the animal and the plant kingdoms. CNG channels have a very complex structure with various subunits and domains that play a critical role in their function. CNG channels are significant in the function of various sensory pathways including vision and olfaction, as well as in other key cellular functions such as hormone release and chemotaxis. CNG channels have also been found to exist in prokaryotes, including many spirochaeta, though their precise role in bacterial physiology remains unknown.
A biochemical cascade, also known as a signaling cascade or signaling pathway, is a series of chemical reactions that occur within a biological cell when initiated by a stimulus. This stimulus, known as a first messenger, acts on a receptor that is transduced to the cell interior through second messengers which amplify the signal and transfer it to effector molecules, causing the cell to respond to the initial stimulus. Most biochemical cascades are series of events, in which one event triggers the next, in a linear fashion. At each step of the signaling cascade, various controlling factors are involved to regulate cellular actions, in order to respond effectively to cues about their changing internal and external environments.
Calcium signaling is the use of calcium ions (Ca2+) to communicate and drive intracellular processes often as a step in signal transduction. Ca2+ is important for cellular signalling, for once it enters the cytosol of the cytoplasm it exerts allosteric regulatory effects on many enzymes and proteins. Ca2+ can act in signal transduction resulting from activation of ion channels or as a second messenger caused by indirect signal transduction pathways such as G protein-coupled receptors.
Human fertilization is the union of a human egg and sperm, occurring primarily in the ampulla of the fallopian tube. The result of this union leads to the production of a fertilized egg called a zygote, initiating embryonic development. Scientists discovered the dynamics of human fertilization in the 19th century.
Veratridine is a steroidal alkaloid found in plants of the lily family, specifically the genera Veratrum and Schoenocaulon. Upon absorption through the skin or mucous membranes, it acts as a neurotoxin by binding to and preventing the inactivation of voltage-gated sodium ion channels in heart, nerve, and skeletal muscle cell membranes. Veratridine increases nerve excitability and intracellular Ca2+ concentrations.
Sperm motility describes the ability of sperm to move properly through the female reproductive tract or through water to reach the egg. Sperm motility can also be thought of as the quality, which is a factor in successful conception; sperm that do not "swim" properly will not reach the egg in order to fertilize it. Sperm motility in mammals also facilitates the passage of the sperm through the cumulus oophorus and the zona pellucida, which surround the mammalian oocyte.
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 encoded by the ABHD2 gene.
CatSper1, is a protein which in humans is encoded by the CATSPER1 gene. CatSper1 is a member of the cation channels of sperm family of protein. The four proteins in this family together form a Ca2+-permeant ion channel specific essential for the correct function of sperm cells.
CatSper2, is a protein which in humans is encoded by the CATSPER2 gene. CatSper2 is a member of the cation channels of sperm family of protein. The four proteins in this family together form a Ca2+-permeant ion channel specific essential for the correct function of sperm cells.
CatSper3, is a protein which in humans is encoded by the CATSPER3 gene. CatSper3 is a member of the cation channels of sperm family of proteins. The four proteins in this family together form a Ca2+-permeant ion channel specific essential for the correct function of sperm cells.
CatSper4, is a protein which in humans is encoded by the CATSPER4 gene. CatSper1 is a member of the cation channels of sperm family of protein. The four proteins in this family together form a Ca2+-permeant ion channel specific essential for the correct function of sperm cells.
Sperm guidance is the process by which sperm cells (spermatozoa) are directed to the oocyte (egg) for the aim of fertilization. In the case of marine invertebrates the guidance is done by chemotaxis. In the case of mammals, it appears to be done by chemotaxis, thermotaxis and rheotaxis.
Sperm chemotaxis is a form of sperm guidance, in which sperm cells (spermatozoa) follow a concentration gradient of a chemoattractant secreted from the oocyte and thereby reach the oocyte.
Oocyteactivation is a series of processes that occur in the oocyte during fertilization.
Sarah Martins da SilvaFRCOG is a British gynaecologist and researcher specialising in male infertility. Martins da Silva is a Clinical Reader in reproductive medicine at the University of Dundee. She also works as an honorary consultant gynaecologist at Ninewells Hospital in Dundee, specialising in fertility problems and assisted conception. She was named one of the BBC's "100 Women of 2019" for her contribution to fertility science.