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Perturbing microtubule integrity blocks AMP-activated protein kinase-induced meiotic resumption in cultured mouse oocytes

Published online by Cambridge University Press:  16 November 2012

Ru Ya  and
Stephen M. Downs
Ru Ya
Affiliation:
Department of Biological Sciences, 530 N 15 St, Marquette University, Milwaukee, WI 5323, USA.
Stephen M. Downs*
Affiliation:
Department of Biological Sciences, 530 N 15 St, Marquette University, Milwaukee, WI 5323, USA.
*
All correspondence to: Stephen M. Downs. Department of Biological Sciences, 530 N 15 St, Marquette University, Milwaukee, WI 5323, USA. Tel: +1 414 288 1698. Fax: +1 414 288 7351. e-mail: stephen.downs@marquette.edu
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Summary

The oocyte meiotic spindle is comprised of microtubules (MT) that bind chromatin and regulate both metaphase plate formation and karyokinesis during meiotic maturation; however, little information is known about their role in meiosis reinitiation. This study was conducted to determine if microtubule integrity is required for meiotic induction and to ascertain how it affects activation of AMP-activated protein kinase (AMPK), an important participant in the meiotic induction process. Treatment with microtubule-disrupting agents nocodazole and vinblastine suppressed meiotic resumption in a dose-dependent manner in both arrested cumulus cell-enclosed oocytes (CEO) stimulated with follicle-stimulating hormone (FSH) and arrested denuded oocytes (DO) stimulated with the AMPK activator, 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR). This effect coincided with suppression of AMPK activation as determined by western blotting and germinal vesicle immunostaining. Treatment with the MT stabilizer paclitaxel also suppressed meiotic induction. Targeting actin filament polymerization had only a marginal effect on meiotic induction. Immunolocalization experiments revealed that active AMPK colocalized with γ-tubulin during metaphase I and II stages, while it localized at the spindle midzone during anaphase. This discrete localization pattern was dependent on MT integrity. Treatment with nocodazole led to disruption of proper spindle pole localization of active AMPK, while paclitaxel induced excessive polymerization of spindle MT and formation of ectopic asters with accentuated AMPK colocalization. Although stimulation of AMPK increased the rate of germinal vesicle breakdown (GVB), spindle formation and polar body (PB) extrusion, the kinase had no effect on peripheral movement of the spindle. These data suggest that the meiosis-inducing action and localization of AMPK are regulated by MT spindle integrity during mouse oocyte maturation.

Keywords

AMPKMeiotic maturationMicrotubulesOocyte
Type
Research Article
Information
Zygote , Volume 22 , Issue 1 , February 2014 , pp. 91 - 102
Copyright
Copyright © Cambridge University Press 2012 

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References

Ai, J.-S., Li, M., Schatten, H. & Sun, Q.-Y. (2009). Regulatory mechanism of spindle movements during oocyte meiotic division. Asian–Aust J. Anim. Sci. 22, 1477–86.CrossRefGoogle Scholar
Albertini, D.F. (1987). Cytoplasmic reorganization during the resumption of meiosis in cultured preovulatory rat oocytes. Dev. Biol. 120, 121–31.CrossRefGoogle Scholar
Albertini, D.F. (1992). Regulation of meiotic maturation in the mammalian oocyte: interplay between exogenous cues and the microtubule cytoskeleton. BioEssays 14, 97–103.CrossRefGoogle ScholarPubMed
Alessi, D.R., Sakamoto, K. & Bayascas, J.R. (2006). LKB1-dependent signaling pathways. Ann. Rev. Biochem. 75, 137–63.CrossRefGoogle ScholarPubMed
Azoury, J., Lee, K. W., Georget, V., Rassinier, P., Leader, B. & Verlhac, M.-H. (2008). Spindle positioning in mouse oocytes relies on a dynamic meshwork of actin filaments. Curr. Biol. 18, 1514–19.CrossRefGoogle ScholarPubMed
Bettencourt-Dias, M., Glet, R., Sinka, R., Mazumdar, A., Lock, W.G., Balloux, F., Zafiropoulos, P.J., Yamaguchi, S., Winter, S., Carthew, R.W., Cooper, M., Jones, D., Frenze, L. & Glover, D.M. (2004). Genome-wide survey of protein kinases required for cell cycle progression. Nature 432, 980–7.CrossRefGoogle Scholar
Bonaccorsi, S., Mottier, V., Giansanti, M.G., Bolkan, B.J., Williams, B., Goldberg, M.L. & Gatti, M. (2007). The Drosophila Lkb1 kinase is required for spindle formation and asymmetric neuroblast division. Development 134, 2183–93.CrossRefGoogle ScholarPubMed
Bultot, L., Horman, S., Neumann, D., Walsh, M. & Hue, L. (2009). Myosin light chains are not a physiological substrate of AMPK in the control of cell structure changes. FEBS Lett. 583, 25–8.CrossRefGoogle Scholar
Campbell, E.M. & Hope, T.J. (2003). Role of the cytoskeleton in nuclear import. Adv. Drug. Deliv. Rev. 55, 761–71.CrossRefGoogle ScholarPubMed
Carling, D. (2004). The AMP-activated protein kinase cascade—a unifying system for energy control. Trends Biochem. Sci. 29, 18–24.CrossRefGoogle ScholarPubMed
Chen, J. & Downs, S. M. (2008). AMP-activated protein kinase is involved in hormone-induced mouse oocyte meiotic maturation in vitro. Dev. Biol. 313, 47–57.CrossRefGoogle ScholarPubMed
Chen, J., Hudson, E., Chi, M. M., Chang, A. S., Moley, K. H., Hardie, D. G. & Downs, S. M. (2006). AMPK regulation of mouse oocyte meiotic resumption in vitro. Dev. Biol. 291, 227–38.CrossRefGoogle ScholarPubMed
Combelles, C.M.H. & Albertini, D.F. (2001). Microtubule patterning during meiotic maturation in mouse oocytes is determined by cell cycle-specific sorting and redistribution of γ-tubulin. Dev. Biol. 239, 281–94.CrossRefGoogle ScholarPubMed
Ding, J., Swain, J.E. & Smith, G.D. (2011). Aurora kinase-A regulates microtubule organizing center (MTOC) localization, chromosome dynamics, and histone-H3 phosphorylation in mouse oocytes. Mol. Reprod. Dev. 78, 80–90.CrossRefGoogle ScholarPubMed
Downs, S.M. (2011). Mouse versus rat: profound differences in meiotic regulation at the level of the isolated oocyte. Mol. Reprod. Dev. 78, 778–94.CrossRefGoogle ScholarPubMed
Downs, S.M. & Chen, J. (2006). Induction of meiotic maturation in mouse oocytes by adenosine analogs. Mol. Reprod. Dev. 73, 1159–68.CrossRefGoogle ScholarPubMed
Downs, S.M., Mosey, J.L. & Klinger, J. (2009). Fatty acid oxidation and meiotic resumption in mouse oocytes. Mol Reprod. Dev. 76, 844–53.CrossRefGoogle ScholarPubMed
Downs, S.M., Ya, R. & Davis, C.C. (2010). Role of AMPK throughout meiotic maturation in the mouse oocyte: evidence for promotion of polar body formation and suppression of premature activation. Mol. Reprod. Dev. 77, 888–99.CrossRefGoogle ScholarPubMed
Dumont, J., Million, K., Sunderland, K., Rassinier, P., Lim, H., Leader, B. & Verlhac, M.-H. (2007). Formin-2 is required for spindle migration and for the late steps of cytokinesis in mouse oocytes. Dev. Biol. 301, 254–65.CrossRefGoogle ScholarPubMed
Giannakakou, P., Sackett, D.L., Ward, Y., Webster, K.R., Blagosklonnyu, M.V. & Fojo, T. (2000). p53 is associated with cellular microtubules and is transported to the nucleus by dynein. Nature Cell Biol. 2, 709–17.CrossRefGoogle ScholarPubMed
Hardie, D.G. (2003). Minireview: the AMP-activated protein kinase cascade: the key sensor of cellular energy status. Endocrinology 144, 5179–83.CrossRefGoogle Scholar
Inoue, M., Naito, K., Nakayama, T. & Sato, E. (1998). Mitogen-activated protein kinase translocates into the germinal vesicle and induces germinal vesicle breakdown in porcine oocytes. Biol. Reprod. 58, 130–6.CrossRefGoogle ScholarPubMed
Jansen, M., Ten Klooster, J.P., Offerhaus, G.J. & Clevers, H. (2009). LKB1 and AMPK family signaling: the intimate link between cell polarity and energy metabolism. Physiol. Rev. 89, 777–98.CrossRefGoogle Scholar
Karaiskou, A., Leprêtre, A.-C., Pahlavan, G., Pasquier, Du, D., Ozon, R. & Jessus, C. (2004). Polo-like kinase confers MPF autoamplification competence to growing Xenopus oocytes. Development 131, 1543–52.CrossRefGoogle ScholarPubMed
Koh, H. & Chung, J. (2007). AMPK links energy status to cell structure and mitosis. Biochem. Biophys. Res. Commun. 362, 789–92.CrossRefGoogle ScholarPubMed
Lam, M.H.C., Thomas, R.J., Loveland, L.K., Schilders, S., Gu, M., Martin, T.J., Gillespie, M.T. & Jans, D.A. (2002). Nuclear transport of parathyroid hormone (PTH)-related protein is dependent on microtubules. Mol. Endocrinol. 16, 390–401.CrossRefGoogle ScholarPubMed
LaRosa, C. & Downs, S.M. (2007). Meiotic induction by heat stress in mouse oocytes: involvement of AMP-activated protein kinase and MAPK family members. Biol. Reprod. 76, 476–86.CrossRefGoogle ScholarPubMed
Lee, J. H., Koh, H., Kim, M., Kim, Y., Lee, S. Y., Karess, R.E., Lee, S.-H., Shong, M., Kim, J.-M., Kim, J. & Chung, J. (2007). Energy-dependent regulation of cell structure by AMP-activated protein kinase. Nature 447, 1017–20.CrossRefGoogle ScholarPubMed
Liu, S.M. and Liu, W.M. (2007). Recent developments in the understanding of nuclear protein import. Protein Peptide Lett. 14, 723–33.CrossRefGoogle ScholarPubMed
Lu, Z., Dunn, R.L., Angeles, R. & Smith, G.D. (2002). Regulation of spindle formation by active mitogen-activated protein kinase and protein phosphatase 2A during mouse oocyte meiosis. Biol. Reprod. 66, 29–37.CrossRefGoogle ScholarPubMed
Ma, C., Cummings, C. & Liu, X. J. (2003). Biphasic activation of aurora-A kinase during the meiosis I–meiosis II transition in Xenopus oocytes. Mol. Cell. Biol. 23, 1703–16.CrossRefGoogle ScholarPubMed
Ma, W., Koch, J. & Vivieros, M.M. (2008). Protein kinase C delta (PKC δ) interacts with microtubule organizing center (MTOC)-associated proteins and participates in meiotic spindle organization. Dev. Biol. 320, 414–25.CrossRefGoogle Scholar
Maro, B., Howlett, S.K. & Webb, M. (1985). Non-spindle microtubule organizing centers in metaphase II-arrested mouse oocytes. J. Cell Biol. 101, 1665–72.CrossRefGoogle ScholarPubMed
Merdes, A., Heald, R., Samejima, K., Earnshaw, W.C. & Cleveland, D.W. (2000). Formation of spindle poles by dynein/dynactin-dependent transport of NuMA. J. Cell Biol. 149, 851–62.CrossRefGoogle ScholarPubMed
Messinger, S.M. & Albertini, D.F. (1991). Centrosome and microtubule dynamics during meiotic progression in mouse oocyte. J. Cell Sci. 100, 289–98.Google ScholarPubMed
Mirouse, V., Swick, L.L., Kazgan, N., St Johnston, D. & Brenman, J.E. (2007). LKB1 and AMPK maintain epithelial cell polarity under energetic stress. J. Cell Biol. 177, 387–92.CrossRefGoogle ScholarPubMed
Na, J. & Zernicka-Goetz, M. (2006). Asymmetric positioning and organization of the meiotic spindle of mouse oocytes requires CDC42 function. Curr. Biol. 16, 1249–54.CrossRefGoogle Scholar
Oh, J.S., Han, S.J. & Conti, M. (2010). Wee1B, Myt1, and Cdc25 function in distinct compartments of the mouse oocyte to control meiotic resumption. J. Cell Biol. 188, 199–207.CrossRefGoogle Scholar
Pines, J. (1999). Four-dimensional control of the cell cycle. Nature Cell Biol. 1, E73–9.CrossRefGoogle Scholar
Rathinasamy, K. & Panda, D. (2008). Kinetic stabilization of microtubule dynamic instability by benomyl increases the nuclear transport of p53. Biochem. Pharmacol. 76, 1669–80.CrossRefGoogle Scholar
Rime, H., Jessus, C. & Ozon, R.. (1988). Estramustine phosphate inhibits germinal vesicle breakdown and induces depolymerization of microtubules in mouse oocyte. Reprod. Nutr. Dev. 28 (2A), 319–34.CrossRefGoogle Scholar
Ruchaud, S., Carmena, M. & Earnshaw, W.C. (2007). Chromosomal passengers: conducting cell division. Nat. Reviews. Mol. Cell Biol. 8, 798–812.CrossRefGoogle ScholarPubMed
Salman, H., Abu-Arish, A., Oliel, S., Loyter, A., Klafter, J., Granek, R. & Elbaum, M. (2005). Nuclear localization signal peptides induce molecular delivery along microtubules. Biophys. J. 89, 2134–45.CrossRefGoogle Scholar
Schatten, H., Schatten, G., Mazia, D., Balczon, R. & Simerly, C. (1986). Behavior of centrosomes during fertilization and cell division in mouse oocytes and sea urchin eggs. Proc. Natl. Acad. Sci. USA 83, 105–9.CrossRefGoogle ScholarPubMed
Stewart, M. (2007). Molecular mechanism of the nuclear protein import cycle. Nature Rev. 8, 195–208.CrossRefGoogle Scholar
Sun, Q.-Y. & Schatten, H. (2006). Regulation of dynamic events by microfilaments during oocyte maturation and fertilization. Reproduction 131, 193–205.CrossRefGoogle Scholar
Sun, S.-C., Xiong, B., Lu, S.-S. & Sun, Q.-Y. (2008). MEK1/2 is a critical regulator of microtubule assembly and spindle organization during rat oocyte meiotic maturation. Mol. Reprod. Dev. 75, 1542–8.CrossRefGoogle ScholarPubMed
Sun, S.-C., Wei, L., Li, M., Lin, S.-L., Xu, B.-Z., Liang, X.-W., Kim, N.-H., Schatten, H., Lu, S.-S. & Sun, Q.-Y. (2009). Perturbation of survivin expression affects chromosome alignment and spindle checkpoint in mouse oocyte meiotic maturation. Cell Cycle 20, 3365–72.CrossRefGoogle Scholar
Szczepańska, K. & Maleszewski, M. (2005). LKB1/PAR4 protein is asymmetrically localized in mouse oocytes and associates with meiotic spindle. Gene Expr. Patterns 6, 86–93.CrossRefGoogle ScholarPubMed
Tong, C., Fan, H.-Y., Lian, L., Li, S.-W., Chen, D.-Y., Schatten, H. & Sun, Q.-Y. (2002). Polo-like kinase-1 is a pivotal regulator of microtubule assembly during mouse oocyte meiotic maturation, fertilization, and early embryonic mitosis. Biol. Reprod. 67, 546–54.CrossRefGoogle ScholarPubMed
Uteng, M., Hentrich, C., Miura, K., Bieling, P. & Surrey, T. (2008). Poleward transport of Eg5 by dynein-dynactin in Xenopus laevis egg extract spindles. J. Cell Biol. 182, 715–26.CrossRefGoogle ScholarPubMed
Uzbekova, S., Arlot-Bonnemains, Y., Dupont, J., Dalbies-Tran, R., Papillier, P., Pennetier, S., Thélie, A. T., Perreau, C., Mermillod, P., Prigent, C. & Uzbekov, R. (2008). Spatio-temporal expression patterns of aurora kinases A, B, and C and cytoplasmic polyadenylation-element-binding protein in bovine oocytes during meiotic maturation. Biol. Reprod. 78, 218–33.CrossRefGoogle ScholarPubMed
Van Blerkom, J. (1991). Microtubule mediation of cytoplasmic and nuclear maturation during the early stages of resumed meiosis in cultured mouse oocytes. Proc. Natl. Acad. Sci. USA 88, 5031–5.CrossRefGoogle ScholarPubMed
Van Blerkom, K. & Bell, H. (1986). Regulation of development in the fully grown mouse oocyte: chromosome-mediated temporal and spatial differentiation of the cytoplasm and plasma membrane. J. Embryol. Exp. Morph. 93, 213–38.Google ScholarPubMed
Vazquez-Martin, A., Oliveras-Ferraros, C. & Menendez, J.A. (2009). The active form of the metabolic sensor: AMP-activated protein kinase (AMPK) directly binds the mitotic apparatus and travels from centrosomes to the spindle midzone during mitosis and cytokinesis. Cell Cycle 8, 2385–98.CrossRefGoogle Scholar
Vazquez-Martin, A., Oliveras-Ferraros, C., Cufi, S. & Menendez, J.A. (2011). Polo-like kinase 1 regulates activation of AMP-activated protein kinase (AMPK) at the mitotic apparatus. Cell Cycle 10, 1295–302.CrossRefGoogle ScholarPubMed
Viveiros, M.M., Hirao, Y. & Eppig, J.J. (2001). Evidence that protein kinase C (PKC) participates in the meiosis I to meiosis II transition in mouse oocytes. Dev. Biol. 235, 330–42.CrossRefGoogle Scholar
Wagstaff, K.M. & Jans, D.A. (2009). Importins and beyond: non-conventional nuclear transport mechanisms. Traffic 10, 1188–98.CrossRefGoogle ScholarPubMed
Wassarman, P.M., Josefowicz, W.J. & Letourneau, G.E. (1976). Meiotic maturation of mouse oocytes in vitro: inhibition of maturation at specific stages of nuclear progression. J. Cell Sci. 22, 531–45.Google ScholarPubMed
Wianny, F., Tayares, A., Evans, M.J., Glover, D.M. & Zernicka-Goetz, M. (1998). Mouse Polo-like kinase 1 associates with the acentriolar spindle poles, meiotic chromosomes and spindle midzone during oocyte maturation. Chromosoma 107, 430–9.CrossRefGoogle ScholarPubMed
Williams, T. & Brenman, J.E. 2008). LKB1 and AMPK in cell polarity and division. Trends Cell Biol. 18, 193–8.CrossRefGoogle ScholarPubMed
Yang, K.T., Li, S.K., Chang, C.C., Tang, C.J.C., Lin, Y.N., Lee, S.C. & Tang, T.K. (2010). Aurora-C kinase deficiency causes cytokinesis failure in meiosis I and production of large polyploid oocytes in mice. Mol. Biol. Cell 21, 2371–83.CrossRefGoogle ScholarPubMed
Yao, L., Zhong, Z., Zhang, L., Chen, D., Schatten, H. & Sun, Q. (2004). Aurora-A is a critical regulator of microtubule assembly and nuclear activity in mouse oocytes, fertilized eggs, and early embryos. Biol. Reprod. 70, 1392–9.CrossRefGoogle Scholar
Yuan, J., Li, M., Wei, L., Yin, S., Xiong, B., Li, S., Lin, S.-L., Schatten, H. & Sun, Q.-Y. (2009). Astrin regulates meiotic spindle organization, spindle pole tethering and cell cycle progression in mouse oocytes. Cell Cycle 8, 3384–95.CrossRefGoogle ScholarPubMed
Zhang, S., Schafer-Hales, K., Khuri, F.R., Zhou, W., Vertino, P.M. & Marcus, A.I. (2008). The tumor suppressor LKB1 regulates lung cancer cell polarity by mediating Cdc42 recruitment and activity. Cancer Res. 68, 740–8.CrossRefGoogle Scholar