Cation channels of sperm

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Cation channels of sperm
Identifiers
SymbolCATSPER
Pfam PF15020
InterPro IPR028246
Membranome 222
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
cation channel, sperm associated 1
Identifiers
SymbolCATSPER1
IUPHAR 388
NCBI gene 117144
HGNC 17116
OMIM 606389
RefSeq NM_053054
UniProt Q8NEC5
Other data
Locus Chr. 11 q12.1
Search for
Structures Swiss-model
Domains InterPro
cation channel, sperm associated 2
Identifiers
SymbolCATSPER2
IUPHAR 389
NCBI gene 117155
HGNC 18810
OMIM 607249
RefSeq NM_172097
UniProt Q96P55
Other data
Locus Chr. 15 q13-q15
Search for
Structures Swiss-model
Domains InterPro
cation channel, sperm associated 3
Identifiers
SymbolCATSPER3
IUPHAR 390
NCBI gene 347732
HGNC 20819
OMIM 609120
RefSeq NM_178019
UniProt Q86XQ3
Other data
Locus Chr. 5 q31.2
Search for
Structures Swiss-model
Domains InterPro
cation channel, sperm associated 4
Identifiers
SymbolCATSPER4
IUPHAR 391
NCBI gene 378807
HGNC 23220
OMIM 609121
RefSeq NM_198137
UniProt Q7RTX7
Other data
Locus Chr. 1 p35.3
Search for
Structures Swiss-model
Domains InterPro

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]

Contents

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]

See also

References

  1. Qi H, Moran MM, Navarro B, Chong JA, Krapivinsky G, Krapivinsky L, et al. (January 2007). "All four CatSper ion channel proteins are required for male fertility and sperm cell hyperactivated motility". Proceedings of the National Academy of Sciences of the United States of America. 104 (4): 1219–23. doi: 10.1073/pnas.0610286104 . PMC   1770895 . PMID   17227845.
  2. Chung JJ, Navarro B, Krapivinsky G, Krapivinsky L, Clapham DE (January 2011). "A novel gene required for male fertility and functional CATSPER channel formation in spermatozoa". Nature Communications. 2 (1): 153. Bibcode:2011NatCo...2..153C. doi:10.1038/ncomms1153. PMC   3999383 . PMID   21224844.
  3. Lishko PV, Botchkina IL, Kirichok Y (March 2011). "Progesterone activates the principal Ca2+ channel of human sperm" . Nature. 471 (7338): 387–91. Bibcode:2011Natur.471..387L. doi:10.1038/nature09767. PMID   21412339. S2CID   4340309.
  4. Miller MR, Mannowetz N, Iavarone AT, Safavi R, Gracheva EO, Smith JF, et al. (April 2016). "Unconventional endocannabinoid signaling governs sperm activation via the sex hormone progesterone". Science. 352 (6285): 555–9. Bibcode:2016Sci...352..555M. doi: 10.1126/science.aad6887 . PMC   5373689 . PMID   26989199.
  5. Sun XH, Zhu YY, Wang L, Liu HL, Ling Y, Li ZL, Sun LB (August 2017). "The Catsper channel and its roles in male fertility: a systematic review". Reproductive Biology and Endocrinology. 15 (1): 65. doi: 10.1186/s12958-017-0281-2 . PMC   5558725 . PMID   28810916.
  6. Carlson AE, Westenbroek RE, Quill T, Ren D, Clapham DE, Hille B, et al. (December 2003). "CatSper1 required for evoked Ca2+ entry and control of flagellar function in sperm". Proceedings of the National Academy of Sciences of the United States of America. 100 (25): 14864–8. Bibcode:2003PNAS..10014864C. doi: 10.1073/pnas.2536658100 . PMC   299831 . PMID   14657352.
  7. Mannowetz N, Miller MR, Lishko PV (May 2017). "Regulation of the sperm calcium channel CatSper by endogenous steroids and plant triterpenoids". Proceedings of the National Academy of Sciences of the United States of America. 114 (22): 5743–5748. Bibcode:2017PNAS..114.5743M. doi: 10.1073/pnas.1700367114 . PMC   5465908 . PMID   28507119.
  8. Miller MR, Kenny SJ, Mannowetz N, Mansell SA, Wojcik M, Mendoza S, et al. (September 2018). "Asymmetrically Positioned Flagellar Control Units Regulate Human Sperm Rotation". Cell Reports. 24 (10): 2606–2613. doi: 10.1016/j.celrep.2018.08.016 . PMC   6177234 . PMID   30184496.
  9. Park EH, Kim DR, Kim HY, Park SK, Chang MS (2014). "Panax ginseng induces the expression of CatSper genes and sperm hyperactivation". Asian Journal of Andrology. 16 (6): 845–51. doi: 10.4103/1008-682X.129129 . PMC   4236327 . PMID   24969054.