TY - JOUR
T1 - Kappa- opioid receptor regulates human sperm functions via SPANX-A/D protein family
AU - Urizar-Arenaza, Itziar
AU - Osinalde, Nerea
AU - Akimov, Vyacheslav
AU - Puglia, Michele
AU - Muñoa-Hoyos, Iraia
AU - Gómez-Giménez, Belén
AU - Gianzo, Marta
AU - Ganzabal, Teresa
AU - Blagoev, Blagoy
AU - Kratchmarova, Irina
AU - Subiran, Nerea
PY - 2020/9
Y1 - 2020/9
N2 - The kappa-opioid receptor (KOR) is involved in the regulation of the fertilizing capacity of human sperm. Recently, a testicular-specific protein family, SPANX-A/D, has also been found to be involved in regulating this process. In order to determine if KOR has a role in the regulation of sperm fertility through the SPANX-A/D protein family, we activated the kappa opioid receptor adding its selective agonist, U50488H to normozoospermic human spermatozoa. Then, we performed immunofluorescence assays and immunoprecipitation experiments followed by LC-MS/MS. According to our results, KOR activation may cause the translocation of SPANX-A/D into the nucleus of human spermatozoa. Phosphoproteomic studies show that KOR does not cause phosphorylation changes in SPANX-A/D residues. However, interactome assays demonstrate that KOR activation provokes changes in SPANX-A/D potential interactors involved in sperm motility, energy metabolism and nuclear processes. Taking these results into account, KOR may regulate human sperm fertility through SPANX-A/D protein family, modifying its subcellular location and interactions. Although further studies are needed, this finding could help us describing the molecular mechanisms underlying sperm fertility as well as developing new strategies for treating infertility.
AB - The kappa-opioid receptor (KOR) is involved in the regulation of the fertilizing capacity of human sperm. Recently, a testicular-specific protein family, SPANX-A/D, has also been found to be involved in regulating this process. In order to determine if KOR has a role in the regulation of sperm fertility through the SPANX-A/D protein family, we activated the kappa opioid receptor adding its selective agonist, U50488H to normozoospermic human spermatozoa. Then, we performed immunofluorescence assays and immunoprecipitation experiments followed by LC-MS/MS. According to our results, KOR activation may cause the translocation of SPANX-A/D into the nucleus of human spermatozoa. Phosphoproteomic studies show that KOR does not cause phosphorylation changes in SPANX-A/D residues. However, interactome assays demonstrate that KOR activation provokes changes in SPANX-A/D potential interactors involved in sperm motility, energy metabolism and nuclear processes. Taking these results into account, KOR may regulate human sperm fertility through SPANX-A/D protein family, modifying its subcellular location and interactions. Although further studies are needed, this finding could help us describing the molecular mechanisms underlying sperm fertility as well as developing new strategies for treating infertility.
KW - Kappa-opioid receptor
KW - SPANX-A/D protein family
KW - Sperm fertility
U2 - 10.1016/j.repbio.2020.07.003
DO - 10.1016/j.repbio.2020.07.003
M3 - Journal article
C2 - 32684427
AN - SCOPUS:85087990686
SN - 1642-431X
VL - 20
SP - 300
EP - 306
JO - Reproductive Biology
JF - Reproductive Biology
IS - 3
ER -