哺乳动物卵母细胞纺锤体的形成及纺锤体检验点的作用机制
|
摘要
染色体精确分离是在纺锤体的正确组装和纺锤体检查点(spindle assembly checkpoint,SAC)的监控下完成的,对于哺乳动物卵母细胞来说,纺锤体的形成和SAC都是保证染色体精确分离的重要因素,如果染色体分离错误将直接导致自发性流产或其他出生缺陷。卵母细胞中心体缺失后,细胞依然能够依靠独立于中心体而围绕染色体成核的微管反向平行排列能形成双极纺锤体,即自我组装纺锤体。由微观组织中心(microtubue organizing center,MTOC)召集微管聚集,成熟促进因子(maturation promoting factor,MPF)维持两次减数分裂过程中纺锤体的形成过程,细胞静止因子(cytostatic factor,CSF)维持分裂中期结构,使纺锤体在染色体没有全部集合到赤道板时保持稳定。大体积的卵母细胞容易产生非整倍体,且卵母细胞中不含有中心体这一特殊性导致卵母细胞中是否存在SAC在很长一段时间内存在争议,但现在SAC是确保卵母细胞染色体精确分离的机制之一已被初步证明。在减数分裂中期染色体之间存在一种黏连,细胞会产生"等待-后期"信号抑制SAC活性,从而保持这种黏连稳定,直至所有染色体完成与纺锤体的连接,"等待-后期"信号失活,SAC启动,使染色体间的黏连失活,进而在纺锤体的作用下染色体分离。作者综述了减数分裂过程中纺锤体的特异性组装过程和纺锤体检查点的组成及作用机制,丰富了减数分裂的相关知识,并为减数分裂过程中非整倍体的形成机制提供依据。
The accurate separation of chromosomes is completed under the correct assembly of spindles and the monitoring of spindle assembly checkpoint(SAC).For the mammalian oocytes,the spindle formation and SAC are the important factors to ensure the accurate separation of chromosomes.If the chromosome is separated incorrectly,it will directly lead to spontaneous abortion or other birth defects.After the oocyte centrosome is deleted,the cells can still form a bipolar spindle by antiparallel arrangement of microtubules which are nucleated around the chromosome independent of the centrosome,that is self-assembled spindle.The microtubules are gathered by the microtubule organization center(MTOC),the maturation promoting factor(MPF) maintains the formation process of the spindle during the two meiosis,and the cytostatic factor(CSF) maintains the metaphase structure,so that the spindle remains stable when the chromosomes do not all converge on the equatorial plate.The heavy volume of sites is prone to aneuploidy,and the particularity that sites don't contain centrosomes leads to a dispute over whether SAC exists on site for a long time,but now SAC is one of the mechanisms to ensure accurate chromosome separation from sites.There is a kind of adhesion between chromosomes in meiosis metaphors,and the ‘wait-later' signal produced by the cell inhibits SAC activity so as to retain the adhesion stable until all chromosomes complete the connection with the spindle,and the ‘wait-later' signal is inactivated,SAC starts to inactivate the adhesion between chromosomes,and then chromosomes are separated under the action of the spindle.This paper reviews the specific assembly process of spindles and the composition and mechanism of spindle checkpoints during meiosis,which enriches our understanding of meiosis and provides a basis of the formation mechanism of aneuploid during meiosis.
The accurate separation of chromosomes is completed under the correct assembly of spindles and the monitoring of spindle assembly checkpoint(SAC).For the mammalian oocytes,the spindle formation and SAC are the important factors to ensure the accurate separation of chromosomes.If the chromosome is separated incorrectly,it will directly lead to spontaneous abortion or other birth defects.After the oocyte centrosome is deleted,the cells can still form a bipolar spindle by antiparallel arrangement of microtubules which are nucleated around the chromosome independent of the centrosome,that is self-assembled spindle.The microtubules are gathered by the microtubule organization center(MTOC),the maturation promoting factor(MPF) maintains the formation process of the spindle during the two meiosis,and the cytostatic factor(CSF) maintains the metaphase structure,so that the spindle remains stable when the chromosomes do not all converge on the equatorial plate.The heavy volume of sites is prone to aneuploidy,and the particularity that sites don't contain centrosomes leads to a dispute over whether SAC exists on site for a long time,but now SAC is one of the mechanisms to ensure accurate chromosome separation from sites.There is a kind of adhesion between chromosomes in meiosis metaphors,and the ‘wait-later' signal produced by the cell inhibits SAC activity so as to retain the adhesion stable until all chromosomes complete the connection with the spindle,and the ‘wait-later' signal is inactivated,SAC starts to inactivate the adhesion between chromosomes,and then chromosomes are separated under the action of the spindle.This paper reviews the specific assembly process of spindles and the composition and mechanism of spindle checkpoints during meiosis,which enriches our understanding of meiosis and provides a basis of the formation mechanism of aneuploid during meiosis.
引文
[1] 朱秀兰,易艳红,唐婷,等.Synaptotagmin1影响小鼠卵母细胞减数分裂和皮质反应的研究[J].生殖医学杂志,2017,26(2):163-167. ZHU X L,YI Y H,TANG T,et al.Synaptotagmin 1 affects meiosis and cortical responses in mouse oocytes[J].Journal of Reproductive Medicine,2017,26(2):163-167.(in Chinese)
[2] HUANG X,WANG J.Mitotic bookmarking:Maintaining the stem cell identity during mitosis[J].Cell Stem Cell,2017,20(6):741-742.
[3] SCHNEIDER I,LéNáRT P.Chromosome segregation:Is the spindle all about microtubules?[J].Current Biology,2017,27(21):1168-1170.
[4] HIRUMA Y,SACRISTAN C,PACHIS S T,et al.Competition between MPS1 and microtubules at kinetochores regulates spindle checkpoint signaling[J].Science,2015,348(6240):1264-1267.
[5] MORRIS E J,DEDHAR S.Stat3 in mitosis:A new role in clustering excess centrosomes[J].Cell Cycle,2017,16(17):1557-1559.
[6] MITRA S.Arabidopsis Cohesin proteins:WAPL,CTF7 and PHD finger proteins:MMDL1,MMDL2 are essential for proper meiosis,gamete development and plant growth[D].Florida:Miami University,2017.
[7] ZHANG T,ZHOU Y,LI L,et al.CenpH regulates meiotic G2/M transition by modulating the APC/CCdh1-cyclin B1 pathway in oocytes[J].Development,2017,144(2):305-312.
[8] 乐祥阳,蒯梦妮,李乾斌,等.新型肿瘤治疗靶点Cdc20的研究进展[J].药学学报,2017,52(9):1366-1371. LE X Y,KUAI M N,LI Q B,et al.Progress in research on the novel cancer therapeutic target Cdc20[J].Journal of Pharmacy,2017,52(9):1366-1371.(in Chinese)
[9] SACRISTAN C,KOPS G J P L.Joined at the hip:Kinetochores,microtubules,and spindle assembly checkpoint signaling[J].Trends in Cell Biology,2015,25(1):21-28.
[10] CRANEY A,KELLY A,JIA L,et al.Control of APC/C-dependent ubiquitin chain elongation by reversible phosphorylation[J].Proceedings of the National Academy of Sciences of the United States of America,2016,113(6):1540-1545.
[11] ZHANG S,CHANG L,ALFIERI C,et al.Molecular mechanism of APC/C activation by mitotic phosphorylation[J].Nature,2016,533(7602):260-264.
[12] DUMONT J,DESAI A.Acentrosomal spindle assembly and chromosome segregation during oocyte meiosis[J].Trends in Cell Biology,2012,22(5):241-249.
[13] RADFORD S J,NGUYEN A L,SCHINDLER K,et al.The chromosomal basis of meiotic acentrosomal spindle assembly and function in oocytes[J].Chromosoma,2017,126(3):351-364.
[14] WANG H Y,JO Y J,SUN T Y,et al.Inhibition of CDK7 bypasses spindle assembly checkpoint via premature cyclin B degradation during oocyte meiosis[J].Biochimica et Biophysica Acta,2016,1863(12):2993-3000.
[15] 孟凡力.运用CALI技术研究中间纺锤体的组装对胞质分裂和有丝分裂退出事件的调控功能[D].南京:南京师范大学,2011. MENG F L.CALI technique was used to study the regulation of cytoplasmic division and mitotic exit events in the assembly of intermediate spindles[D].Nanjing:Nanjing normal University,2011.(in Chinese)
[16] SEVERSON A F,VON DASSOW G,BOWERMAN B.Oocyte meiotic spindle assembly and function[M].Current Topics in Developmental Biology,2016,116:65-98.
[17] BATTAGLIA D E,GOODWIN P,KLEIN N A,et al.Fertilization and early embryology:Influence of maternal age on meiotic spindle assembly oocytes from naturally cycling women[J].Human Reproduction,1996,11(10):2217-2222.
[18] ARIAS TORRES A J,BüHLER M S,ZELARAYáN L I. In vitro steroid-induced meiosis in Rhinella arenarum oocytes:Role of pre-MPF activation[J].Zygote,2016,24(2):252-258.
[19] SCHUH M,ELLENBERG J.Self-organization of MTOCs replaces centrosome function during acentrosomal spindle assembly in live mouse oocytes[J].Cell,2007,130(3):484-498.
[20] 陈长超,王令怡,孙嘉豪,等.秋水仙碱对猪卵母细胞成熟及MⅠ期纺锤体的影响[J].南京农业大学学报,2016,39(5):825-830. CHEN C C,WANG L Y,SUN J H,et al.Effects of colchicine on the M Ⅰ spindle structure and in vitro maturation of porcine oocytes[J].Journal of Nanjing Agricultural University,2016,39(5):825-830.(in Chinese)
[21] LEE H S,KIM K H,KIM E Y,et al.Obox4-silencing-activated STAT3 and MPF/MAPK signaling accelerate nuclear membrane breakdown in mouse oocytes[J].Reproduction,2016,151(4):369-378.
[22] KONCICKA M,TETKOVA A,JANSOVA D,et al.Increased expression of maturation promoting factor components speeds up meiosis in oocytes from aged females[J].International Journal of Molecular Sciences,2018,19(9):2841.
[23] TIWARI M,CHAUBE S K.Maturation promoting factor destabilization mediates human chorionic gonadotropin induced meiotic resumption in rat oocytes[J].Development Growth & Differentiation,2017,59(7):603-614.
[24] SUN W,LIU C,FENG Y,et al.Macrophage colony-stimulating factor (M-CSF) is an intermediate in the process of luteinizing hormone-induced decrease in natriuretic peptide receptor 2 (NPR2) and resumption of oocyte meiosis[J].Journal of Ovarian Research,2017,10(1):68.
[25] KALOUS J,TETKOVA A,KUBELKA M,et al.Importance of ERK1/2 in regulation of protein translation during oocyte meiosis[J].International Journal of Molecular Sciences,2018,19(3):E698.
[26] TSENG T L.Factors influencing the processing of VDE-induced DNA double-strand breaks during meiosis[D].England:University of Sheffield,2015.
[27] LIAO Y,LIN D,CUI P,et al.Polo-like kinase 1 inhibition results in misaligned chromosomes and aberrant spindles in porcine oocytes during the first meiotic division[J].Reproduction in Domestic Animals,2018,53(1):256-265.
[28] WANG H,JO Y J,OH J S,et al.Quercetin delays postovulatory aging of mouse oocytes by regulating SIRT expression and MPF activity[J].Oncotarget,2017,8(24):38631-38641.
[29] BERTOLINI S,WANG B,MEIER B,et al.Caenorhabditis elegans BUB-3 and SAN-1/MAD3 spindle assembly checkpoint components are required for genome stability in response to treatment with ionizing radiation[J].Genes Genomes Genetics,2017,7(12):3875-3885.
[30] SUN S C,KIM N H.Spindle assembly checkpoint and its regulators in meiosis[J].Human Reproduction Update,2011,18(1):60-72.
[31] WANG W H,SUN Q Y.Meiotic spindle,spindle checkpoint and embryonic aneuploidy[J].Frontiers in Bioscience,2006,11:620-636.
[32] MUSACCHIO A.The molecular biology of spindle assembly checkpoint signaling dynamics[J].Current Biology,2015,25(20):1002-1018.
[33] COURTHEOUX T,DIALLO A,DAMODARAN A P,et al.Aurora A kinase activity is required to maintain an active spindle assembly checkpoint during prometaphase[J].Journal of Cell Science,2018,131(7):191353.
[34] RAAIJMAKERS J A,VAN HEESBEEN R G H P,BLOMEN V A,et al.BUB1 is essential for the viability of human cells in which the spindle assembly checkpoint is compromised[J].Cell Reports,2018,22(6):1424-1438.
[35] ALFIERI C,CHANG L,ZHANG Z,et al.Molecular basis of APC/C regulation by the spindle assembly checkpoint[J].Nature,2016,536(7617):431-436.
[36] XIE Y,WANG A,LIN J,et al.Mps1/TTK:A novel target and biomarker for cancer[J].Journal of Drug Targeting,2017,25(2):112-118.
[37] OVERLACK K,KRENN V,MUSACCHIO A.When mad met bub[J].EMBO Reports,2014,15(4):326-328.
[38] YUAN Y F,REN Y X,YUAN P,et al.TRAIP is involved in chromosome alignment and SAC regulation in mouse oocyte meiosis[J].Scientific Reports,2016,6:29735.
[39] STRAUSS B,HARRISON A,COELHO P A,et al.Cyclin B1 is essential for mitosis in mouse embryos,and its nuclear export sets the time for mitosis[J].Journal of Molecular Cell Biology,2018,217(1):179-193.
[2] HUANG X,WANG J.Mitotic bookmarking:Maintaining the stem cell identity during mitosis[J].Cell Stem Cell,2017,20(6):741-742.
[3] SCHNEIDER I,LéNáRT P.Chromosome segregation:Is the spindle all about microtubules?[J].Current Biology,2017,27(21):1168-1170.
[4] HIRUMA Y,SACRISTAN C,PACHIS S T,et al.Competition between MPS1 and microtubules at kinetochores regulates spindle checkpoint signaling[J].Science,2015,348(6240):1264-1267.
[5] MORRIS E J,DEDHAR S.Stat3 in mitosis:A new role in clustering excess centrosomes[J].Cell Cycle,2017,16(17):1557-1559.
[6] MITRA S.Arabidopsis Cohesin proteins:WAPL,CTF7 and PHD finger proteins:MMDL1,MMDL2 are essential for proper meiosis,gamete development and plant growth[D].Florida:Miami University,2017.
[7] ZHANG T,ZHOU Y,LI L,et al.CenpH regulates meiotic G2/M transition by modulating the APC/CCdh1-cyclin B1 pathway in oocytes[J].Development,2017,144(2):305-312.
[8] 乐祥阳,蒯梦妮,李乾斌,等.新型肿瘤治疗靶点Cdc20的研究进展[J].药学学报,2017,52(9):1366-1371. LE X Y,KUAI M N,LI Q B,et al.Progress in research on the novel cancer therapeutic target Cdc20[J].Journal of Pharmacy,2017,52(9):1366-1371.(in Chinese)
[9] SACRISTAN C,KOPS G J P L.Joined at the hip:Kinetochores,microtubules,and spindle assembly checkpoint signaling[J].Trends in Cell Biology,2015,25(1):21-28.
[10] CRANEY A,KELLY A,JIA L,et al.Control of APC/C-dependent ubiquitin chain elongation by reversible phosphorylation[J].Proceedings of the National Academy of Sciences of the United States of America,2016,113(6):1540-1545.
[11] ZHANG S,CHANG L,ALFIERI C,et al.Molecular mechanism of APC/C activation by mitotic phosphorylation[J].Nature,2016,533(7602):260-264.
[12] DUMONT J,DESAI A.Acentrosomal spindle assembly and chromosome segregation during oocyte meiosis[J].Trends in Cell Biology,2012,22(5):241-249.
[13] RADFORD S J,NGUYEN A L,SCHINDLER K,et al.The chromosomal basis of meiotic acentrosomal spindle assembly and function in oocytes[J].Chromosoma,2017,126(3):351-364.
[14] WANG H Y,JO Y J,SUN T Y,et al.Inhibition of CDK7 bypasses spindle assembly checkpoint via premature cyclin B degradation during oocyte meiosis[J].Biochimica et Biophysica Acta,2016,1863(12):2993-3000.
[15] 孟凡力.运用CALI技术研究中间纺锤体的组装对胞质分裂和有丝分裂退出事件的调控功能[D].南京:南京师范大学,2011. MENG F L.CALI technique was used to study the regulation of cytoplasmic division and mitotic exit events in the assembly of intermediate spindles[D].Nanjing:Nanjing normal University,2011.(in Chinese)
[16] SEVERSON A F,VON DASSOW G,BOWERMAN B.Oocyte meiotic spindle assembly and function[M].Current Topics in Developmental Biology,2016,116:65-98.
[17] BATTAGLIA D E,GOODWIN P,KLEIN N A,et al.Fertilization and early embryology:Influence of maternal age on meiotic spindle assembly oocytes from naturally cycling women[J].Human Reproduction,1996,11(10):2217-2222.
[18] ARIAS TORRES A J,BüHLER M S,ZELARAYáN L I. In vitro steroid-induced meiosis in Rhinella arenarum oocytes:Role of pre-MPF activation[J].Zygote,2016,24(2):252-258.
[19] SCHUH M,ELLENBERG J.Self-organization of MTOCs replaces centrosome function during acentrosomal spindle assembly in live mouse oocytes[J].Cell,2007,130(3):484-498.
[20] 陈长超,王令怡,孙嘉豪,等.秋水仙碱对猪卵母细胞成熟及MⅠ期纺锤体的影响[J].南京农业大学学报,2016,39(5):825-830. CHEN C C,WANG L Y,SUN J H,et al.Effects of colchicine on the M Ⅰ spindle structure and in vitro maturation of porcine oocytes[J].Journal of Nanjing Agricultural University,2016,39(5):825-830.(in Chinese)
[21] LEE H S,KIM K H,KIM E Y,et al.Obox4-silencing-activated STAT3 and MPF/MAPK signaling accelerate nuclear membrane breakdown in mouse oocytes[J].Reproduction,2016,151(4):369-378.
[22] KONCICKA M,TETKOVA A,JANSOVA D,et al.Increased expression of maturation promoting factor components speeds up meiosis in oocytes from aged females[J].International Journal of Molecular Sciences,2018,19(9):2841.
[23] TIWARI M,CHAUBE S K.Maturation promoting factor destabilization mediates human chorionic gonadotropin induced meiotic resumption in rat oocytes[J].Development Growth & Differentiation,2017,59(7):603-614.
[24] SUN W,LIU C,FENG Y,et al.Macrophage colony-stimulating factor (M-CSF) is an intermediate in the process of luteinizing hormone-induced decrease in natriuretic peptide receptor 2 (NPR2) and resumption of oocyte meiosis[J].Journal of Ovarian Research,2017,10(1):68.
[25] KALOUS J,TETKOVA A,KUBELKA M,et al.Importance of ERK1/2 in regulation of protein translation during oocyte meiosis[J].International Journal of Molecular Sciences,2018,19(3):E698.
[26] TSENG T L.Factors influencing the processing of VDE-induced DNA double-strand breaks during meiosis[D].England:University of Sheffield,2015.
[27] LIAO Y,LIN D,CUI P,et al.Polo-like kinase 1 inhibition results in misaligned chromosomes and aberrant spindles in porcine oocytes during the first meiotic division[J].Reproduction in Domestic Animals,2018,53(1):256-265.
[28] WANG H,JO Y J,OH J S,et al.Quercetin delays postovulatory aging of mouse oocytes by regulating SIRT expression and MPF activity[J].Oncotarget,2017,8(24):38631-38641.
[29] BERTOLINI S,WANG B,MEIER B,et al.Caenorhabditis elegans BUB-3 and SAN-1/MAD3 spindle assembly checkpoint components are required for genome stability in response to treatment with ionizing radiation[J].Genes Genomes Genetics,2017,7(12):3875-3885.
[30] SUN S C,KIM N H.Spindle assembly checkpoint and its regulators in meiosis[J].Human Reproduction Update,2011,18(1):60-72.
[31] WANG W H,SUN Q Y.Meiotic spindle,spindle checkpoint and embryonic aneuploidy[J].Frontiers in Bioscience,2006,11:620-636.
[32] MUSACCHIO A.The molecular biology of spindle assembly checkpoint signaling dynamics[J].Current Biology,2015,25(20):1002-1018.
[33] COURTHEOUX T,DIALLO A,DAMODARAN A P,et al.Aurora A kinase activity is required to maintain an active spindle assembly checkpoint during prometaphase[J].Journal of Cell Science,2018,131(7):191353.
[34] RAAIJMAKERS J A,VAN HEESBEEN R G H P,BLOMEN V A,et al.BUB1 is essential for the viability of human cells in which the spindle assembly checkpoint is compromised[J].Cell Reports,2018,22(6):1424-1438.
[35] ALFIERI C,CHANG L,ZHANG Z,et al.Molecular basis of APC/C regulation by the spindle assembly checkpoint[J].Nature,2016,536(7617):431-436.
[36] XIE Y,WANG A,LIN J,et al.Mps1/TTK:A novel target and biomarker for cancer[J].Journal of Drug Targeting,2017,25(2):112-118.
[37] OVERLACK K,KRENN V,MUSACCHIO A.When mad met bub[J].EMBO Reports,2014,15(4):326-328.
[38] YUAN Y F,REN Y X,YUAN P,et al.TRAIP is involved in chromosome alignment and SAC regulation in mouse oocyte meiosis[J].Scientific Reports,2016,6:29735.
[39] STRAUSS B,HARRISON A,COELHO P A,et al.Cyclin B1 is essential for mitosis in mouse embryos,and its nuclear export sets the time for mitosis[J].Journal of Molecular Cell Biology,2018,217(1):179-193.