#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Selective Disruption of Aurora C Kinase Reveals Distinct Functions from Aurora B Kinase during Meiosis in Mouse Oocytes


Aurora B kinase (AURKB) is the catalytic subunit of the chromosomal passenger complex (CPC), an essential regulator of chromosome segregation. In mitosis, the CPC is required to regulate kinetochore microtubule (K-MT) attachments, the spindle assembly checkpoint, and cytokinesis. Germ cells express an AURKB homolog, AURKC, which can also function in the CPC. Separation of AURKB and AURKC function during meiosis in oocytes by conventional approaches has not been successful. Therefore, the meiotic function of AURKC is still not fully understood. Here, we describe an ATP-binding-pocket-AURKC mutant, that when expressed in mouse oocytes specifically perturbs AURKC-CPC and not AURKB-CPC function. Using this mutant we show for the first time that AURKC has functions that do not overlap with AURKB. These functions include regulating localized CPC activity and regulating chromosome alignment and K-MT attachments at metaphase of meiosis I (Met I). We find that AURKC-CPC is not the sole CPC complex that regulates the spindle assembly checkpoint in meiosis, and as a result most AURKC-perturbed oocytes arrest at Met I. A small subset of oocytes do proceed through cytokinesis normally, suggesting that AURKC-CPC is not the sole CPC complex during telophase I. But, the resulting eggs are aneuploid, indicating that AURKC is a critical regulator of meiotic chromosome segregation in female gametes. Taken together, these data suggest that mammalian oocytes contain AURKC to efficiently execute meiosis I and ensure high-quality eggs necessary for sexual reproduction.


Vyšlo v časopise: Selective Disruption of Aurora C Kinase Reveals Distinct Functions from Aurora B Kinase during Meiosis in Mouse Oocytes. PLoS Genet 10(2): e32767. doi:10.1371/journal.pgen.1004194
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004194

Souhrn

Aurora B kinase (AURKB) is the catalytic subunit of the chromosomal passenger complex (CPC), an essential regulator of chromosome segregation. In mitosis, the CPC is required to regulate kinetochore microtubule (K-MT) attachments, the spindle assembly checkpoint, and cytokinesis. Germ cells express an AURKB homolog, AURKC, which can also function in the CPC. Separation of AURKB and AURKC function during meiosis in oocytes by conventional approaches has not been successful. Therefore, the meiotic function of AURKC is still not fully understood. Here, we describe an ATP-binding-pocket-AURKC mutant, that when expressed in mouse oocytes specifically perturbs AURKC-CPC and not AURKB-CPC function. Using this mutant we show for the first time that AURKC has functions that do not overlap with AURKB. These functions include regulating localized CPC activity and regulating chromosome alignment and K-MT attachments at metaphase of meiosis I (Met I). We find that AURKC-CPC is not the sole CPC complex that regulates the spindle assembly checkpoint in meiosis, and as a result most AURKC-perturbed oocytes arrest at Met I. A small subset of oocytes do proceed through cytokinesis normally, suggesting that AURKC-CPC is not the sole CPC complex during telophase I. But, the resulting eggs are aneuploid, indicating that AURKC is a critical regulator of meiotic chromosome segregation in female gametes. Taken together, these data suggest that mammalian oocytes contain AURKC to efficiently execute meiosis I and ensure high-quality eggs necessary for sexual reproduction.


Zdroje

1. HassoldT, ChiuD (1985) Maternal age-specific rates of numerical chromosome abnormalities with special reference to trisomy. Hum Genet 70: 11–17.

2. HassoldT, HallH, HuntP (2007) The origin of human aneuploidy: where we have been, where we are going. Hum Mol Genet 16 Spec No. 2: R203–208.

3. HassoldT, HuntP (2001) To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2: 280–291.

4. LelandS, NagarajanP, PolyzosA, ThomasS, SamaanG, et al. (2009) Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice. Proc Natl Acad Sci U S A 106: 12776–12781.

5. JonesKT (2008) Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with age. Hum Reprod Update 14: 143–158.

6. YangKT, LiSK, ChangCC, TangCJ, LinYN, et al. (2010) Aurora-C kinase deficiency causes cytokinesis failure in meiosis I and production of large polyploid oocytes in mice. Mol Biol Cell 21: 2371–2383.

7. ChiangT, DuncanFE, SchindlerK, SchultzRM, LampsonMA (2010) Evidence that weakened centromere cohesion is a leading cause of age-related aneuploidy in oocytes. Curr Biol 20: 1522–1528.

8. DavydenkoO, SchultzRM, LampsonMA (2013) Increased CDK1 activity determines the timing of kinetochore-microtubule attachments in meiosis I. J Cell Biol 202: 221–229.

9. HomerHA, McDougallA, LevasseurM, MurdochAP, HerbertM (2005) Mad2 is required for inhibiting securin and cyclin B degradation following spindle depolymerisation in meiosis I mouse oocytes. Reproduction 130: 829–843.

10. LaneSI, YunY, JonesKT (2012) Timing of anaphase-promoting complex activation in mouse oocytes is predicted by microtubule-kinetochore attachment but not by bivalent alignment or tension. Development 139: 1947–1955.

11. CarmenaM, WheelockM, FunabikiH, EarnshawWC (2012) The chromosomal passenger complex (CPC): from easy rider to the godfather of mitosis. Nat Rev Mol Cell Biol 13: 789–803.

12. NicklasRB (1997) How cells get the right chromosomes. Science 275: 632–637.

13. MaldonadoM, KapoorTM (2011) Constitutive Mad1 targeting to kinetochores uncouples checkpoint signalling from chromosome biorientation. Nat Cell Biol 13: 475–482.

14. MatsonDR, DemirelPB, StukenbergPT, BurkeDJ (2012) A conserved role for COMA/CENP-H/I/N kinetochore proteins in the spindle checkpoint. Genes Dev 26: 542–547.

15. Murata-HoriM, FumotoK, FukutaY, IwasakiT, KikuchiA, et al. (2000) Myosin II regulatory light chain as a novel substrate for AIM-1, an aurora/Ipl1p-related kinase from rat. J Biochem 128: 903–907.

16. ToureA, MzaliR, LiotC, SeguinL, MorinL, et al. (2008) Phosphoregulation of MgcRacGAP in mitosis involves Aurora B and Cdk1 protein kinases and the PP2A phosphatase. FEBS Lett 582: 1182–1188.

17. SharifB, NaJ, Lykke-HartmannK, McLaughlinSH, LaueE, et al. (2010) The chromosome passenger complex is required for fidelity of chromosome transmission and cytokinesis in meiosis of mouse oocytes. J Cell Sci 123: 4292–4300.

18. RuchaudS, CarmenaM, EarnshawWC (2007) Chromosomal passengers: conducting cell division. Nat Rev Mol Cell Biol 8: 798–812.

19. KellyAE, FunabikiH (2009) Correcting aberrant kinetochore microtubule attachments: an Aurora B-centric view. Curr Opin Cell Biol 21: 51–58.

20. van der WaalMS, HengeveldRC, van der HorstA, LensSM (2012) Cell division control by the Chromosomal Passenger Complex. Exp Cell Res 318: 1407–1420.

21. TsengTC, ChenSH, HsuYP, TangTK (1998) Protein kinase profile of sperm and eggs: cloning and characterization of two novel testis-specific protein kinases (AIE1, AIE2) related to yeast and fly chromosome segregation regulators. DNA Cell Biol 17: 823–833.

22. ChenHL, TangCJ, ChenCY, TangTK (2005) Overexpression of an Aurora-C kinase-deficient mutant disrupts the Aurora-B/INCENP complex and induces polyploidy. J Biomed Sci 12: 297–310.

23. SchindlerK, DavydenkoO, FramB, LampsonMA, SchultzRM (2012) Maternally recruited Aurora C kinase is more stable than Aurora B to support mouse oocyte maturation and early development. Proc Natl Acad Sci U S A 109: E2215–2222.

24. ShudaK, SchindlerK, MaJ, SchultzRM, DonovanPJ (2009) Aurora kinase B modulates chromosome alignment in mouse oocytes. Mol Reprod Dev 76: 1094–1105.

25. SwainJE, DingJ, WuJ, SmithGD (2008) Regulation of spindle and chromatin dynamics during early and late stages of oocyte maturation by aurora kinases. Mol Hum Reprod 14: 291–299.

26. HondaR, KornerR, NiggEA (2003) Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis. Mol Biol Cell 14: 3325–3341.

27. SasaiK, KatayamaH, StenoienDL, FujiiS, HondaR, et al. (2004) Aurora-C kinase is a novel chromosomal passenger protein that can complement Aurora-B kinase function in mitotic cells. Cell Motil Cytoskeleton 59: 249–263.

28. LiX, SakashitaG, MatsuzakiH, SugimotoK, KimuraK, et al. (2004) Direct association with inner centromere protein (INCENP) activates the novel chromosomal passenger protein, Aurora-C. J Biol Chem 279: 47201–47211.

29. Fernandez-MirandaG, TrakalaM, MartinJ, EscobarB, GonzalezA, et al. (2011) Genetic disruption of aurora B uncovers an essential role for aurora C during early mammalian development. Development 138: 2661–2672.

30. LaneSI, ChangHY, JenningsPC, JonesKT (2010) The Aurora kinase inhibitor ZM447439 accelerates first meiosis in mouse oocytes by overriding the spindle assembly checkpoint. Reproduction 140: 521–530.

31. HengeveldRC, HertzNT, VromansMJ, ZhangC, BurlingameAL, et al. (2012) Development of a chemical genetic approach for human aurora B kinase identifies novel substrates of the chromosomal passenger complex. Mol Cell Proteomics 11: 47–59.

32. MortlockAA, FooteKM, HeronNM, JungFH, PasquetG, et al. (2007) Discovery, synthesis, and in vivo activity of a new class of pyrazoloquinazolines as selective inhibitors of aurora B kinase. J Med Chem 50: 2213–2224.

33. VogtE, KippA, Eichenlaub-RitterU (2009) Aurora kinase B, epigenetic state of centromeric heterochromatin and chiasma resolution in oocytes. Reprod Biomed Online 19: 352–368.

34. ChenSH, TangTK (2002) Mutational analysis of the phosphorylation sites of the Aie1 (Aurora-C) kinase in vitro. DNA Cell Biol 21: 41–46.

35. GarskeAL, PetersU, CortesiAT, PerezJL, ShokatKM (2011) Chemical genetic strategy for targeting protein kinases based on covalent complementarity. Proc Natl Acad Sci U S A 108: 15046–15052.

36. ZhangC, KenskiDM, PaulsonJL, BonshtienA, SessaG, et al. (2005) A second-site suppressor strategy for chemical genetic analysis of diverse protein kinases. Nat Methods 2: 435–441.

37. WangF, UlyanovaNP, DaumJR, PatnaikD, KatenevaAV, et al. (2012) Haspin inhibitors reveal centromeric functions of Aurora B in chromosome segregation. J Cell Biol 199: 251–268.

38. NakajimaY, CormierA, TyersRG, PigulaA, PengY, et al. (2011) Ipl1/Aurora-dependent phosphorylation of Sli15/INCENP regulates CPC-spindle interaction to ensure proper microtubule dynamics. J Cell Biol 194: 137–153.

39. DitchfieldC, JohnsonVL, TigheA, EllstonR, HaworthC, et al. (2003) Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. J Cell Biol 161: 267–280.

40. SunSC, WeiL, LiM, LinSL, XuBZ, et al. (2009) Perturbation of survivin expression affects chromosome alignment and spindle checkpoint in mouse oocyte meiotic maturation. Cell Cycle 8: 3365–3372.

41. SunSC, LiuHL, SunQY (2012) Survivin regulates Plk1 localization to kinetochore in mouse oocyte meiosis. Biochem Biophys Res Commun 421: 797–800.

42. WangF, UlyanovaNP, van der WaalMS, PatnaikD, LensSM, et al. (2011) A positive feedback loop involving Haspin and Aurora B promotes CPC accumulation at centromeres in mitosis. Curr Biol 21: 1061–1069.

43. SchindlerK, SchultzRM (2009) CDC14B acts through FZR1 (CDH1) to prevent meiotic maturation of mouse oocytes. Biol Reprod 80: 795–803.

44. GuiL, HomerH (2012) Spindle assembly checkpoint signalling is uncoupled from chromosomal position in mouse oocytes. Development 139: 1941–1946.

45. KhodjakovA, PinesJ (2010) Centromere tension: a divisive issue. Nat Cell Biol 12: 919–923.

46. MusacchioA, SalmonED (2007) The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol 8: 379–393.

47. BrunetS, PahlavanG, TaylorS, MaroB (2003) Functionality of the spindle checkpoint during the first meiotic division of mammalian oocytes. Reproduction 126: 443–450.

48. McGuinnessBE, AngerM, KouznetsovaA, Gil-BernabeAM, HelmhartW, et al. (2009) Regulation of APC/C activity in oocytes by a Bub1-dependent spindle assembly checkpoint. Curr Biol 19: 369–380.

49. GirdlerF, GascoigneKE, EyersPA, HartmuthS, CrafterC, et al. (2006) Validating Aurora B as an anti-cancer drug target. J Cell Sci 119: 3664–3675.

50. VigneronS, PrietoS, BernisC, LabbeJC, CastroA, et al. (2004) Kinetochore localization of spindle checkpoint proteins: who controls whom? Mol Biol Cell 15: 4584–4596.

51. SteinP, SchindlerK (2011) Mouse oocyte microinjection, maturation and ploidy assessment. J Vis Exp 53: pii: 2851.

52. BrunetS, MariaAS, GuillaudP, DujardinD, KubiakJZ, et al. (1999) Kinetochore fibers are not involved in the formation of the first meiotic spindle in mouse oocytes, but control the exit from the first meiotic M phase. J Cell Biol 146: 1–12.

53. LampsonMA, RenduchitalaK, KhodjakovA, KapoorTM (2004) Correcting improper chromosome-spindle attachments during cell division. Nat Cell Biol 6: 232–237.

54. JellumaN, BrenkmanAB, van den BroekNJ, CruijsenCW, van OschMH, et al. (2008) Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignment. Cell 132: 233–246.

55. RiederCL (1981) The structure of the cold-stable kinetochore fiber in metaphase PtK1 cells. Chromosoma 84: 145–158.

56. HuHM, ChuangCK, LeeMJ, TsengTC, TangTK (2000) Genomic organization, expression, and chromosome localization of a third aurora-related kinase gene, Aie1. DNA Cell Biol 19: 679–688.

57. Ben KhelifaM, ZouariR, HarbuzR, HalouaniL, ArnoultC, et al. (2011) A new AURKC mutation causing macrozoospermia: implications for human spermatogenesis and clinical diagnosis. Mol Hum Reprod 17: 762–768.

58. SantaguidaS, VernieriC, VillaF, CilibertoA, MusacchioA (2011) Evidence that Aurora B is implicated in spindle checkpoint signalling independently of error correction. EMBO J 30: 1508–1519.

59. FamulskiJK, ChanGK (2007) Aurora B kinase-dependent recruitment of hZW10 and hROD to tensionless kinetochores. Curr Biol 17: 2143–2149.

60. BirkenfeldJ, NalbantP, BohlBP, PertzO, HahnKM, et al. (2007) GEF-H1 modulates localized RhoA activation during cytokinesis under the control of mitotic kinases. Dev Cell 12: 699–712.

61. QiM, YuW, LiuS, JiaH, TangL, et al. (2005) Septin1, a new interaction partner for human serine/threonine kinase aurora-B. Biochem Biophys Res Commun 336: 994–1000.

62. XuZ, VagnarelliP, OgawaH, SamejimaK, EarnshawWC (2010) Gradient of increasing Aurora B kinase activity is required for cells to execute mitosis. J Biol Chem 285: 40163–40170.

63. LahamLE, MukhopadhyayN, RobertsTM (2000) The activation loop in Lck regulates oncogenic potential by inhibiting basal kinase activity and restricting substrate specificity. Oncogene 19: 3961–3970.

64. Garcia-ParamioP, CabrerizoY, BornancinF, ParkerPJ (1998) The broad specificity of dominant inhibitory protein kinase C mutants infers a common step in phosphorylation. Biochem J 333(Pt 3): 631–636.

65. HuJ, YuH, KornevAP, ZhaoJ, FilbertEL, et al. (2011) Mutation that blocks ATP binding creates a pseudokinase stabilizing the scaffolding function of kinase suppressor of Ras, CRAF and BRAF. Proc Natl Acad Sci U S A 108: 6067–6072.

66. BoudeauJ, Miranda-SaavedraD, BartonGJ, AlessiDR (2006) Emerging roles of pseudokinases. Trends Cell Biol 16: 443–452.

67. KimminsS, CrosioC, KotajaN, HirayamaJ, MonacoL, et al. (2007) Differential functions of the Aurora-B and Aurora-C kinases in mammalian spermatogenesis. Mol Endocrinol 21: 726–739.

68. KimuraM, MatsudaY, YoshiokaT, OkanoY (1999) Cell cycle-dependent expression and centrosome localization of a third human aurora/Ipl1-related protein kinase, AIK3. J Biol Chem 274: 7334–7340.

69. LewandoskiM, WassarmanKM, MartinGR (1997) Zp3-cre, a transgenic mouse line for the activation or inactivation of loxP-flanked target genes specifically in the female germ line. Curr Biol 7: 148–151.

70. IgarashiH, KnottJG, SchultzRM, WilliamsCJ (2007) Alterations of PLCbeta1 in mouse eggs change calcium oscillatory behavior following fertilization. Dev Biol 312: 321–330.

71. SchultzRM, MontgomeryRR, BelanoffJR (1983) Regulation of mouse oocyte meiotic maturation: implication of a decrease in oocyte cAMP and protein dephosphorylation in commitment to resume meiosis. Dev Biol 97: 264–273.

72. TsafririA, ChunSY, ZhangR, HsuehAJ, ContiM (1996) Oocyte maturation involves compartmentalization and opposing changes of cAMP levels in follicular somatic and germ cells: studies using selective phosphodiesterase inhibitors. Dev Biol 178: 393–402.

73. LampsonMA, KapoorTM (2005) The human mitotic checkpoint protein BubR1 regulates chromosome-spindle attachments. Nat Cell Biol 7: 93–98.

74. SalimianKJ, BallisterER, SmoakEM, WoodS, PanchenkoT, et al. (2011) Feedback control in sensing chromosome biorientation by the Aurora B kinase. Curr Biol 21: 1158–1165.

75. DuncanFE, ChiangT, SchultzRM, LampsonMA (2009) Evidence that a defective spindle assembly checkpoint is not the primary cause of maternal age-associated aneuploidy in mouse eggs. Biol Reprod 81: 768–776.

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2014 Číslo 2
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#