Cation channels of sperm explained

cation channel, sperm associated 1
Hgncid:17116
Symbol:CATSPER1
Iuphar Id:yes
Entrezgene:117144
Omim:606389
Refseq:NM_053054
Uniprot:Q8NEC5
Chromosome:11
Arm:q
Band:12.1
cation channel, sperm associated 2
Hgncid:18810
Symbol:CATSPER2
Iuphar Id:yes
Entrezgene:117155
Omim:607249
Refseq:NM_172097
Uniprot:Q96P55
Chromosome:15
Arm:q
Band:13
Locussupplementarydata:-q15
cation channel, sperm associated 3
Hgncid:20819
Symbol:CATSPER3
Iuphar Id:yes
Entrezgene:347732
Omim:609120
Refseq:NM_178019
Uniprot:Q86XQ3
Chromosome:5
Arm:q
Band:31.2
cation channel, sperm associated 4
Hgncid:23220
Symbol:CATSPER4
Iuphar Id:yes
Entrezgene:378807
Omim:609121
Refseq:NM_198137
Uniprot:Q7RTX7
Chromosome:1
Arm:p
Band:35.3

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

External links

Notes and References

  1. Qi H, Moran MM, Navarro B, Chong JA, Krapivinsky G, Krapivinsky L, Kirichok Y, Ramsey IS, Quill TA, Clapham DE . 6 . 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 . January 2007 . 17227845 . 1770895 . 10.1073/pnas.0610286104 . free .
  2. Chung JJ, Navarro B, Krapivinsky G, Krapivinsky L, Clapham DE . A novel gene required for male fertility and functional CATSPER channel formation in spermatozoa . Nature Communications . 2 . 153 . January 2011 . 1 . 21224844 . 3999383 . 10.1038/ncomms1153 . 2011NatCo...2..153C .
  3. Lishko PV, Botchkina IL, Kirichok Y . Progesterone activates the principal Ca2+ channel of human sperm . Nature . 471 . 7338 . 387–91 . March 2011 . 21412339 . 10.1038/nature09767 . 2011Natur.471..387L . 4340309 .
  4. Miller MR, Mannowetz N, Iavarone AT, Safavi R, Gracheva EO, Smith JF, Hill RZ, Bautista DM, Kirichok Y, Lishko PV . 6 . Unconventional endocannabinoid signaling governs sperm activation via the sex hormone progesterone . Science . 352 . 6285 . 555–9 . April 2016 . 26989199 . 10.1126/science.aad6887 . 5373689 . 2016Sci...352..555M . free .
  5. Sun XH, Zhu YY, Wang L, Liu HL, Ling Y, Li ZL, Sun LB . The Catsper channel and its roles in male fertility: a systematic review . Reproductive Biology and Endocrinology . 15 . 1 . 65 . August 2017 . 28810916 . 5558725 . 10.1186/s12958-017-0281-2 . free .
  6. Carlson AE, Westenbroek RE, Quill T, Ren D, Clapham DE, Hille B, Garbers DL, Babcock DF . 6 . 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 . December 2003 . 14657352 . 299831 . 10.1073/pnas.2536658100 . 2003PNAS..10014864C . free .
  7. Mannowetz N, Miller MR, Lishko PV . 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 . May 2017 . 28507119 . 5465908 . 10.1073/pnas.1700367114. 2017PNAS..114.5743M . free .
  8. Miller MR, Kenny SJ, Mannowetz N, Mansell SA, Wojcik M, Mendoza S, Zucker RS, Xu K, Lishko PV . 6 . Asymmetrically Positioned Flagellar Control Units Regulate Human Sperm Rotation . en . Cell Reports . 24 . 10 . 2606–2613 . September 2018 . 30184496 . 10.1016/j.celrep.2018.08.016 . 6177234 . free .
  9. Park EH, Kim DR, Kim HY, Park SK, Chang MS . Panax ginseng induces the expression of CatSper genes and sperm hyperactivation . Asian Journal of Andrology . 16 . 6 . 845–51 . 2014 . 24969054 . 4236327 . 10.4103/1008-682X.129129 . free .