Mitogen-activated protein kinase-activated protein kinase 2 is a critical regulator of pig oocyte meiotic maturation
Xiang-Hong Ou A D , Sen Li A , Bao-Zeng Xu B C , Lei-Ning Chen A , Man-Xi Jiang A , Shao-Qin Chen A and Nan-Qiao Chen A
+ Author Affiliations
- Author Affiliations
A Reproductive Medicine Center, The 2nd People’s Hospital of Guangdong Province, #1 Shiliuguang RD, Haizhou, Guangzhou, 510317, China.
B Institute of Special Wild Economic Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Jilin, China.
C Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
D Corresponding author. Email: ouxianghong2003@163.com
Reproduction, Fertility and Development 29(2) 223-233 https://doi.org/10.1071/RD15150
Submitted: 15 April 2015 Accepted: 16 June 2015 Published: 21 July 2015
Abstract
Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2), a direct substrate of p38 MAPK, plays key roles in multiple cellular processes. In the present study, we showed that MK2 affected not only cumulus expansion, but also the oocyte meiotic cell cycle in porcine oocytes. Inhibition of MK2 arrested oocytes at the germinal vesicle (GV) stage or the prometaphase I/metaphase I stage. Unlike in mouse oocytes, where phosphorylated (p-) MK2 was localised at the minus end of spindle microtubules and close to the spindle poles, in porcine oocytes p-MK2 was concentrated at the spindle equator and localised at the plus end of spindle microtubules. Knockdown or inhibition of MK2 resulted in spindle defects: spindles were surrounded by irregular chromosome non-disjunction or by chromosomes detached from the spindles. MK2 regulated spindle organisation and chromosome alignment by connecting microtubules with kinetochores. In addition, unlike in mitotic cells and meiotic mouse oocytes, the MK2–p38 MAPK pathway may not play an important role during meiotic cell cycle in porcine oocytes. In conclusion, MK2 is an important regulator of porcine oocyte meiotic maturation.
Additional keywords: chromosome, meiosis, spindle.
References
Ashraf, M. I., Ebner, M., Wallner, C., Haller, M., Khalid, S., Schwelberger, H., Koziel, K., Enthammer, M., Hermann, M., Sickinger, S., Soleiman, A., Steger, C., Vallant, S., Sucher, R., Brandacher, G., Santer, P., Dragun, D., and Troppmair, J. (2014). A p38 MAPK/MK2 signaling pathway leading to redox stress, cell death and ischemia/reperfusion injury. Cell Commun. Signal. 12, 6.| A p38 MAPK/MK2 signaling pathway leading to redox stress, cell death and ischemia/reperfusion injury.Crossref | GoogleScholarGoogle Scholar | 24423080PubMed |
Ben-Levy, R., Hooper, S., Wilson, R., Paterson, H. F., and Marshall, C. J. (1998). Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2. Curr. Biol. 8, 1049–1057.
| Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXmsVGktr0%3D&md5=539a2cd99480d934edf27c73fe7ab373CAS | 9768359PubMed |
Davidson, W., Frego, L., Peet, G. W., Kroe, R. R., Labadia, M. E., Lukas, S. M., Snow, R. J., Jakes, S., Grygon, C. A., Pargellis, C., and Werneburg, B. G. (2004). Discovery and characterization of a substrate selective p38alpha inhibitor. Biochemistry 43, 11 658–11 671.
| Discovery and characterization of a substrate selective p38alpha inhibitor.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXmvFSrtbs%3D&md5=967f874004b6a900b2dd90bd05c5c8ecCAS |
Deng, M., Gao, J., Suraneni, P., and Li, R. (2009). Kinetochore-independent chromosome poleward movement during anaphase of meiosis II in mouse eggs. PLoS One 4, e5249.
| Kinetochore-independent chromosome poleward movement during anaphase of meiosis II in mouse eggs.Crossref | GoogleScholarGoogle Scholar | 19365562PubMed |
Fan, H. Y., and Sun, Q. Y. (2004). Involvement of mitogen-activated protein kinase cascade during oocyte maturation and fertilization in mammals. Biol. Reprod. 70, 535–547.
| Involvement of mitogen-activated protein kinase cascade during oocyte maturation and fertilization in mammals.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhs1Chsro%3D&md5=d953c4ee422509f0927a6bb93d8fcc85CAS | 14613897PubMed |
Fan, H. Y., Liu, Z., Shimada, M., Sterneck, E., Johnson, P. F., Hedrick, S. M., and Richards, J. S. (2009). MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for female fertility. Science 324, 938–941.
| MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for female fertility.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXlslWnu74%3D&md5=c83dd25debdfd06978c65fa6f91a01dcCAS | 19443782PubMed |
Farghaly, T., Khalifa, E., Mostafa, S., Hussein, M., Bedaiwy, M., and Ahmady, A. (2015). The effect of temporary meiotic attenuation on the in vitro maturation outcome of bovine oocytes. In Vitro Cell. Dev. Biol. Anim. , .
| The effect of temporary meiotic attenuation on the in vitro maturation outcome of bovine oocytes.Crossref | GoogleScholarGoogle Scholar | 25784604PubMed |
Garcia-Cruz, R., Brieno, M. A., Roig, I., Grossmann, M., Velilla, E., Pujol, A., Cabero, L., Pessarrodona, A., Barbero, J. L., and Garcia Caldes, M. (2010). Dynamics of cohesin proteins REC8, STAG3, SMC1 beta and SMC3 are consistent with a role in sister chromatid cohesion during meiosis in human oocytes. Hum. Reprod. 25, 2316–2327.
| Dynamics of cohesin proteins REC8, STAG3, SMC1 beta and SMC3 are consistent with a role in sister chromatid cohesion during meiosis in human oocytes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtVGru77J&md5=a8942d1a252cd6222aad0a45ccfae20aCAS | 20634189PubMed |
Goncharov, B. F., and Skoblina, M. N. (2014). [Nonhormonal stimulation in vitro of oocyte maturation in sturgeons.] Ontogenez 45, 102–111.
| 1:STN:280:DC%2BC2Mrpt1eitw%3D%3D&md5=e9ca3715ada20e11c2c7aa102b515e67CAS | 25720268PubMed |
Jin, S., Zhang, M., Lei, L., Wang, C., Fu, M., Ning, G., and Xia, G. (2006). Meiosis activating sterol (MAS) regulate FSH-induced meiotic resumption of cumulus cell-enclosed porcine oocytes via PKC pathway. Mol. Cell. Endocrinol. 249, 64–70.
| Meiosis activating sterol (MAS) regulate FSH-induced meiotic resumption of cumulus cell-enclosed porcine oocytes via PKC pathway.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XjvVWmtL0%3D&md5=a671468bbfc2ef5acffcc852e7a3bcf3CAS | 16500744PubMed |
Kahyaoglu, I., Demir, B., Turkkani, A., Cinar, O., Dilbaz, S., Dilbaz, B., and Mollamahmutoglu, L. (2014). Total fertilization failure: is it the end of the story? J. Assist. Reprod. Genet. 31, 1155–1160.
| Total fertilization failure: is it the end of the story?Crossref | GoogleScholarGoogle Scholar | 24962788PubMed |
Kawashima, I., Liu, Z., Mullany, L. K., Mihara, T., Richards, J. S., and Shimada, M. (2012). EGF-like factors induce expansion of the cumulus cell–oocyte complexes by activating calpain-mediated cell movement. Endocrinology 153, 3949–3959.
| EGF-like factors induce expansion of the cumulus cell–oocyte complexes by activating calpain-mediated cell movement.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtFGktbvF&md5=94e10d47ba745b5353a8f71f1fae6ad7CAS | 22673225PubMed |
Kitajima, T. S., Ohsugi, M., and Ellenberg, J. (2011). Complete kinetochore tracking reveals error-prone homologous chromosome biorientation in mammalian oocytes. Cell 146, 568–581.
| Complete kinetochore tracking reveals error-prone homologous chromosome biorientation in mammalian oocytes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtVKjsbzL&md5=3e9cb501572106ab9d3b638fd1fdb95bCAS | 21854982PubMed |
Lee, J., Okada, K., Ogushi, S., Miyano, T., Miyake, M., and Yamashita, M. (2006). Loss of Rec8 from chromosome arm and centromere region is required for homologous chromosome separation and sister chromatid separation, respectively, in mammalian meiosis. Cell Cycle 5, 1448–1455.
| Loss of Rec8 from chromosome arm and centromere region is required for homologous chromosome separation and sister chromatid separation, respectively, in mammalian meiosis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XpvF2qs70%3D&md5=bc26a51f471511a8ed859396aeda62d2CAS | 16855401PubMed |
Ou, X. H., Li, S., Xu, B. Z., Wang, Z. B., Quan, S., Li, M., Zhang, Q. H., Ouyang, Y. C., Schatten, H., Xing, F. Q., and Sun, Q. Y. (2010). p38alpha MAPK is a MTOC-associated protein regulating spindle assembly, spindle length and accurate chromosome segregation during mouse oocyte meiotic maturation. Cell Cycle 9, 4130–4143.
| p38alpha MAPK is a MTOC-associated protein regulating spindle assembly, spindle length and accurate chromosome segregation during mouse oocyte meiotic maturation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXit1ahur0%3D&md5=7cefcf7782d8943d01f6561b5d0fe783CAS | 20948319PubMed |
Reinhardt, H. C., Aslanian, A. S., Lees, J. A., and Yaffe, M. B. (2007). p53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38 MAPK/MK2 pathway for survival after DNA damage. Cancer Cell 11, 175–189.
| p53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38 MAPK/MK2 pathway for survival after DNA damage.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXitVartLc%3D&md5=3bf266a9212516b9b7168dc1612470acCAS | 17292828PubMed |
Salustri, A., and Siracusa, G. (1983). Metabolic coupling, cumulus expansion and meiotic resumption in mouse cumuli oophori cultured in vitro in the presence of FSH or dcAMP, or stimulated in vivo by hCG. J. Reprod. Fertil. 68, 335–341.
| Metabolic coupling, cumulus expansion and meiotic resumption in mouse cumuli oophori cultured in vitro in the presence of FSH or dcAMP, or stimulated in vivo by hCG.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL3sXks1Clu7g%3D&md5=500ef0c9c5ea0a8f29e3ee5131243fb6CAS | 6306235PubMed |
Sumara, I., Vorlaufer, E., Stukenberg, P. T., Kelm, O., Redemann, N., Nigg, E. A., and Peters, J. M. (2002). The dissociation of cohesin from chromosomes in prophase is regulated by Polo-like kinase. Mol. Cell 9, 515–525.
| The dissociation of cohesin from chromosomes in prophase is regulated by Polo-like kinase.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XivVyltrY%3D&md5=335641363e867824ac99ccefa431d99eCAS | 11931760PubMed |
Sun, Q. Y., Rubinstein, S., and Breitbart, H. (1999). MAP kinase activity is downregulated by phorbol ester during mouse oocyte maturation and egg activation in vitro. Mol. Reprod. Dev. 52, 310–318.
| MAP kinase activity is downregulated by phorbol ester during mouse oocyte maturation and egg activation in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXpsFantQ%3D%3D&md5=98f7698473e9ccf509d8102c122f28c8CAS | 10206663PubMed |
Sun, Q. Y., Lai, L., Wu, G. M., Park, K. W., Day, B. N., Prather, R. S., and Schatten, H. (2001). Microtubule assembly after treatment of pig oocytes with taxol: correlation with chromosomes, gamma-tubulin, and MAP kinase. Mol. Reprod. Dev. 60, 481–490.
| Microtubule assembly after treatment of pig oocytes with taxol: correlation with chromosomes, gamma-tubulin, and MAP kinase.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXosl2qt74%3D&md5=6079a76ce9f1b9c0ad942adb23521032CAS | 11746959PubMed |
Sun, Q. Y., Miao, Y. L., and Schatten, H. (2009). Towards a new understanding on the regulation of mammalian oocyte meiosis resumption. Cell Cycle 8, 2741–2747.
| Towards a new understanding on the regulation of mammalian oocyte meiosis resumption.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXkslWitLw%3D&md5=e6794b6a93f5f0b3246dc844110d9f58CAS | 19717979PubMed |
Tang, J., Yang, X., and Liu, X. (2008). Phosphorylation of Plk1 at Ser326 regulates its functions during mitotic progression. Oncogene 27, 6635–6645.
| Phosphorylation of Plk1 at Ser326 regulates its functions during mitotic progression.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtlegurfK&md5=6fb2938abb966c6cf2b5091487041c40CAS | 18695677PubMed |
ter Haar, E., Prabhakar, P., Liu, X., and Lepre, C. (2007). Crystal structure of the p38 alpha–MAPKAP kinase 2 heterodimer. J. Biol. Chem. 282, 9733–9739.
| Crystal structure of the p38 alpha–MAPKAP kinase 2 heterodimer.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXjtlCiur4%3D&md5=585787e8528404faf210fe8c49bffbc6CAS | 17255097PubMed |
Tosca, L., Crochet, S., Ferre, P., Foufelle, F., Tesseraud, S., and Dupont, J. (2006). AMP-activated protein kinase activation modulates progesterone secretion in granulosa cells from hen preovulatory follicles. J. Endocrinol. 190, 85–97.
| AMP-activated protein kinase activation modulates progesterone secretion in granulosa cells from hen preovulatory follicles.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XnvFaksb8%3D&md5=1359bbcf445a5a459e1088370a1da8fdCAS | 16837613PubMed |
Villa-Diaz, L. G., and Miyano, T. (2004). Activation of p38 MAPK during porcine oocyte maturation. Biol. Reprod. 71, 691–696.
| Activation of p38 MAPK during porcine oocyte maturation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXmtFWgu7Y%3D&md5=335cef209b96a9eda77bd7f03d70c860CAS | 15115730PubMed |
Xu, B. Z., Li, M., Xiong, B., Lin, S. L., Zhu, J. Q., Hou, Y., Chen, D. Y., and Sun, Q. Y. (2009). Involvement of calcium/calmodulin-dependent protein kinase kinase in meiotic maturation of pig oocytes. Anim. Reprod. Sci. 111, 17–30.
| Involvement of calcium/calmodulin-dependent protein kinase kinase in meiotic maturation of pig oocytes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhsFCgs7%2FL&md5=7f13fa43e897fbf63381d8dd1adc3030CAS | 18367350PubMed |
Yuan, J., Xu, B. Z., Qi, S. T., Tong, J. S., Wei, L., Li, M., Ouyang, Y. C., Hou, Y., Schatten, H., and Sun, Q. Y. (2010). MAPK-activated protein kinase 2 is required for mouse meiotic spindle assembly and kinetochore-microtubule attachment. PLoS One 5, e11247.
| MAPK-activated protein kinase 2 is required for mouse meiotic spindle assembly and kinetochore-microtubule attachment.Crossref | GoogleScholarGoogle Scholar | 20596525PubMed |
