The chromosomal basis of meiotic acentrosomal spindle assembly and function in oocytes

Radford, Sarah J.; Nguyen, Alexandra L.; Schindler, Karen; McKim, Kim S.

doi:10.1007/s00412-016-0618-1

Cited by 37 publications

(39 citation statements)

References 147 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mammalian oocytes also have an extended period of dynamic KT-MT interactions [58], lasting 6-8 hours in mice and up to 16 hours in human [59,60]. All of these results are in line with our conclusion that oocytes require PP1-87B to prevent premature stable KT-MT attachments and avoiding cohesion fatigue.…”

Section: The Transition Of Sister Centromeres From Co-orientation To supporting

confidence: 88%

Cohesin and microtubule dependent mechanisms regulate sister centromere fusion during meiosis I

McKim

Wang

Das

2019

Preprint

Self Cite

View full text Add to dashboard Cite

Sister centromere fusion is a process unique to meiosis that promotes co-orientation of the sister kinetochores, ensuring they attach to microtubules from the same pole. We have found that the kinetochore protein SPC105R/KNL1 and Protein Phosphatase 1 (PP1-87B) are required for this process. The analysis of these two proteins, however, has shown that two independent mechanisms maintain sister centromere fusion during meiosis I in Drosophila oocytes. Double depletion experiments demonstrated that the precocious separation of centromeres in Spc105RRNAi oocytes is Separase-dependent, suggesting cohesin proteins must be maintained at the core centromeres. In contrast, precocious sister centromere separation in Pp1-87B RNAi oocytes does not depend on Separase or Wapl. Further analysis with microtubule destabilizing drugs showed that PP1-87B maintains sister centromeres fusion by regulating microtubule dynamics.Additional double depletion experiments demonstrated that PP1-87B has this function by antagonizing Polo kinase and BubR1, two proteins known to promote kinetochore-microtubule (KT-MT) attachments. These results suggest that PP1-87B maintains sister centromere fusion by inhibiting stable KT-MT attachments. Surprisingly, we found that loss of C(3)G, the transverse element of the synaptonemal complex (SC), suppresses centromere separation in Pp1-87B RNAi oocytes. This is evidence for a functional role of centromeric SC in the meiotic divisions. We propose two mechanisms maintain co-orientation in Drosophila oocytes: one involves SPC105R to protect cohesins at sister centromeres and another involves PP1-87B to regulate spindle forces at end-on attachments. Author SummaryMeiosis involves two cell divisions. In the first division, pairs of homologous chromosomes segregate, in the second division, the sister chromatids segregate. These patterns of division are mediated by regulating microtubule attachments to the kinetochores and stepwise release of cohesion between the sister chromatids. During meiosis I, cohesion fusing sister centromeres must be intact so they attach to microtubules from the same pole. At the same time, arm cohesion must be released for anaphase I. Upon entry into meiosis II, the sister centromeres must separate to allow attachment to opposite poles, while cohesion surrounding the centromeres must remain intact until anaphase II. How these different populations of cohesion are regulated is not understood. We identified two genes required for maintaining sister centromere cohesion, and surprisingly found they define two distinct mechanisms. The first is a kinetochore protein that maintains sister centromere fusion by recruiting proteins that protect cohesion. The second is a phosphatase that antagonizes proteins that stabilize microtubule attachments. We propose that entry into meiosis II coincides with stabilization of microtubule attachments, resulting in the separation of sister centromeres without disrupting cohesion in other regions, facilitating attachment of sister chromatids to opposite poles.

show abstract

Section: The Transition Of Sister Centromeres From Co-orientation To supporting

confidence: 88%

Cohesin and microtubule dependent mechanisms regulate sister centromere fusion during meiosis I

McKim

Wang

Das

2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…congression (46,49). Therefore, spindle and chromosome abnormalities are always accompanied by errors in kinetochore-microtubule attachments (50)(51)(52). We then assessed the stability of kinetochore-microtubule attachments after cool treatment that depolymerizes microtubules that are unattached to kinetochores.…”

Section: Discussionmentioning

confidence: 99%

BaP exposure causes oocyte meiotic arrest and fertilization failure to weaken female fertility

et al. 2017

View full text Add to dashboard Cite

Benzo[a]pyrene (BaP) is a ubiquitous environmental pollutant and carcinogen that is frequently found in particulate matter, with a diameter of ≤2.5 μm (PM2.5). It has been reported to interrupt the normal reproductive system, but the exact molecular basis has not been clearly defined. To understand the underlying mechanisms regarding how BaP exposure disrupts female fertility, we evaluated oocyte quality by assessing the critical regulators and events during oocyte meiotic maturation and fertilization. We found that BaP exposure compromised the mouse oocyte meiotic progression by disrupting normal spindle assembly, chromosome alignment, and kinetochore-microtubule attachment, consequently leading to the generation of aneuploid eggs. In addition, BaP administration significantly decreased the fertilization rate of mouse eggs by reducing the number of sperm binding to the zona pellucida, which was consistent with the premature cleavage of N terminus of zona pellucida sperm-binding protein 2 and precocious exocytosis of ovastacin. Furthermore, BaP exposure interfered with the gamete fusion process by perturbing the localization and protein level of Juno. Notably, we found that BaP exposure induced oxidative stress with an increased level of reactive oxygen species and apoptosis in oocytes and thereby led to the deterioration of critical regulators and events during oocyte meiotic progression and fertilization. Our data document that BaP exposure reduces female fertility impairing oocyte maturation and fertilization ability induced by oxidative stress and early apoptosis in murine models.-Zhang, M., Miao, Y., Chen, Q., Cai, M., Dong, W., Dai, X., Lu, Y., Zhou, C., Cui, Z., Xiong, B. BaP exposure causes oocyte meiotic arrest and fertilization failure to weaken female fertility.

show abstract

“…In simple terms, chromosomes switch on Subito-dependent nucleation, while this pathway remains switched off in the cytoplasm of the oocyte. Ran-GTP or Aurora B activity could potentially act as the signal from the meiotic chromosomes to remove auto-inhibition of Subito (Bennabi et al, 2016; Radford et al, 2017). Taken together, tight regulation of Subito appears critical to assemble spindle microtubules around the chromosomes and to prevent their assembly anywhere else.…”

Section: Discussionmentioning

confidence: 99%

A novel microtubule nucleation pathway for meiotic spindle assembly in oocytes

Romé

Ohkura

2018

Preprint

View full text Add to dashboard Cite

1The meiotic spindle in oocytes is assembled in the absence of centrosomes, the major 2 microtubule nucleation sites in mitotic and male meiotic cells. A crucial, yet unresolved 3 question in meiosis is how spindle microtubules are generated without centrosomes and 4 only around chromosomes in the large volume of oocytes. Here we report a novel oocyte-5 specific microtubule nucleation pathway that is essential for assembling most spindle 6 microtubules complementarily with the Augmin pathway, and sufficient for triggering 7 microtubule assembly in oocytes. This pathway is mediated by the kinesin-6 Subito/MKlp2, 8 which recruits the γ-tubulin complex to the spindle equator to nucleate microtubules in 9 Drosophila oocytes. Away from chromosomes, Subito interaction with the γ-tubulin complex 10 is suppressed by its N-terminal region to prevent ectopic microtubule assembly in oocytes. 11We further demonstrate that the Subito complex from ovaries can nucleate microtubules 12 from pure tubulin dimers in vitro. Taken together, microtubule nucleation regulated by 13Subito drives spatially restricted spindle assembly in oocytes.14 15 not peer-reviewed)

show abstract

The chromosomal basis of meiotic acentrosomal spindle assembly and function in oocytes

Cited by 37 publications

References 147 publications

Cohesin and microtubule dependent mechanisms regulate sister centromere fusion during meiosis I

Cohesin and microtubule dependent mechanisms regulate sister centromere fusion during meiosis I

BaP exposure causes oocyte meiotic arrest and fertilization failure to weaken female fertility

A novel microtubule nucleation pathway for meiotic spindle assembly in oocytes

Contact Info

Product

Resources

About