Cation channels of sperm
Identifiers
SymbolCATSPER
PfamPF15020
InterProIPR028246
Membranome222
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
cation channel, sperm associated 1
Identifiers
SymbolCATSPER1
IUPHAR388
NCBI gene117144
HGNC17116
OMIM606389
RefSeqNM_053054
UniProtQ8NEC5
Other data
LocusChr. 11 q12.1
Search for
StructuresSwiss-model
DomainsInterPro
cation channel, sperm associated 2
Identifiers
SymbolCATSPER2
IUPHAR389
NCBI gene117155
HGNC18810
OMIM607249
RefSeqNM_172097
UniProtQ96P55
Other data
LocusChr. 15 q13-q15
Search for
StructuresSwiss-model
DomainsInterPro
cation channel, sperm associated 3
Identifiers
SymbolCATSPER3
IUPHAR390
NCBI gene347732
HGNC20819
OMIM609120
RefSeqNM_178019
UniProtQ86XQ3
Other data
LocusChr. 5 q31.2
Search for
StructuresSwiss-model
DomainsInterPro
cation channel, sperm associated 4
Identifiers
SymbolCATSPER4
IUPHAR391
NCBI gene378807
HGNC23220
OMIM609121
RefSeqNM_198137
UniProtQ7RTX7
Other data
LocusChr. 1 p35.3
Search for
StructuresSwiss-model
DomainsInterPro

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]

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.
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