Aurora kinase-A regulates microtubule organizing center (MTOC) localization, chromosome dynamics, and histone-H3 phosphorylation in mouse oocytes

We previously isolated Aurora-C/Aie1 in a screen for kinases expressed in mouse sperm and eggs. Here, we show the localization of endogenous Aurora-C and examine its roles during female mouse meiosis. Aurora-C was detected at the centromeres and along the chromosome arms in prometaphase I–metaphase I and was concentrated at centromeres at metaphase II, in which Aurora-C also was phosphorylated at Thr171. During the anaphase I–telophase I transition, Aurora-C was dephosphorylated and relocalized to the midzone and midbody. Microinjection of the kinase-deficient Aurora-C (AurC-KD) mRNA into mouse oocytes significantly inhibited Aurora-C activity and caused multiple defects, including chromosome misalignment, abnormal kinetochore–microtubule attachment, premature chromosome segregation, and cytokinesis failure in meiosis I. Furthermore, AurC-KD reduced Aurora-C and histone H3 phosphorylation and inhibited kinetochore localization of Bub1 and BubR1. Similar effects also were observed in the oocytes injected with INCNEP-delIN mRNAs, in which the Aurora-C binding motif was removed. The most dramatic effect observed in AurC-KD–injected oocytes is cytokinesis failure in meiosis I, resulting in producing large polyploid oocytes, a pattern similar to Aurora-C deficiency human spermatozoa. Surprisingly, we detected no Aurora-B protein in mouse oocytes. We propose that Aurora-C, but not Aurora-B, plays essential roles in female mouse meiosis.

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CEP215 and AURKA regulate spindle pole focusing and aMTOC organization in mouse oocytes

Reproduction ◽

10.1530/rep-19-0263 ◽

2020 ◽

Vol 159 (3) ◽

pp. 261-274

Author(s):

Xiaotian Wang ◽

Claudia Baumann ◽

Rabindranath De La Fuente ◽

Maria M Viveiros

Keyword(s):

Critical Role ◽

Super Resolution ◽

Aurora Kinase ◽

Spindle Pole ◽

Meiotic Spindle ◽

Dependent Manner ◽

Aurora Kinase A ◽

Mouse Oocytes ◽

Kinase A

Acentriolar microtubule-organizing centers (aMTOCs) play a critical role in stable meiotic spindle assembly in oocytes, necessary for accurate chromosome segregation. Yet, there is a limited understanding of the essential regulatory components of these unique MTOCs. In somatic cells, CEP215 (Centrosomal Protein 215) serves as an important regulator of centrosome maturation and spindle organization. Here, we assessed whether it has a similar function in mouse oocytes. CEP215 was detected in oocyte lysates and specifically localized to aMTOCs throughout the progression of meiosis in a pericentrin-dependent manner. Super-resolution microscopy revealed CEP215 co-localization with pericentrin and a unique pore/ring-like structural organization of aMTOCs. Interestingly, inhibition of Aurora Kinase A in either MI or MII-stage oocytes resulted in a striking loss of the ring-like aMTOC organization and pronounced CEP215 clustering at spindle poles, as well as shorter spindles with highly focused poles. In vitro siRNA-mediated transcript knockdown effectively reduced CEP215 in approximately 85% of the oocytes. Maturation rates to MII were similar in the Cep215 siRNA and injected controls; however, a high percentage (~40%) of the Cep215-knockdown oocytes showed notable variations in spindle pole focusing. Surprisingly, pericentrin and γ-tubulin localization and fluorescence intensity at aMTOCs were unaltered in knockdown oocytes, contrasting with mitotic cells where CEP215 depletion reduced γ-tubulin at centrosomes. Our results demonstrate that CEP215 is a functional component of oocyte aMTOCs and participates in the regulation of meiotic spindle pole focusing. Moreover, these studies reveal a vital role for Aurora Kinase A activity in the maintenance of aMTOC organization in oocytes.

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Nocturnal Activation of Aurora C in Rat Pineal Gland: Its Role in the Norepinephrine-Induced Phosphorylation of Histone H3 and Gene Expression

Endocrinology ◽

10.1210/en.2008-1507 ◽

2008 ◽

Vol 150 (5) ◽

pp. 2334-2341 ◽

Cited By ~ 12

Author(s):

D. M. Price ◽

R. Kanyo ◽

N. Steinberg ◽

C. L. Chik ◽

A. K. Ho

Keyword(s):

Protein Kinase ◽

Pineal Gland ◽

Protein Kinase A ◽

Histone H3 ◽

Time Profile ◽

Mitotic Kinase ◽

H3 Phosphorylation ◽

Histone H3 Phosphorylation ◽

Rat Pineal Gland ◽

Kinase A

We have shown previously that Ser10 phosphorylation of histone H3 occurs in rat pinealocytes after stimulation with norepinephrine (NE) and that histone modifications such as acetylation appear to play an important role in pineal gene transcription. Here we report the nocturnal phosphorylation of a Ser10 histone H3 kinase, Aurora C, in the rat pineal gland. The time profile of this phosphorylation parallels the increase in the level of phospho-Ser10 histone H3. Studies with cultured pinealocytes indicate that Aurora C phosphorylation is induced by NE and this induction can be blocked by cotreatment with propranolol or KT5720, a protein kinase A inhibitor. Moreover, only treatment with dibutyryl cAMP, but not other kinase activators, mimics the effect of NE on Aurora C phosphorylation. These results indicate that Aurora C is phosphorylated primarily by a β-adrenergic/protein kinase A-mediated mechanism. Treatment with an Aurora C inhibitor reduces the NE-induced histone H3 phosphorylation and suppresses the NE-stimulated induction of arylalkylamine N-acetyltransferase (AA-NAT), the rhythm-controlling enzyme of melatonin synthesis, and melatonin production. The effects of Aurora C inhibitors on adrenergic-induced genes in rat pinealocytes are gene specific: inhibitory for Aa-nat and inducible cAMP repressor but stimulatory for c-fos. Together our results support a role for the NE-stimulated phosphorylation of Aurora C and the subsequent remodeling of chromatin in NE-stimulated Aa-nat transcription. This phenomenon suggests that activation of this mitotic kinase can be induced by extracellular signals to participate in the transcriptional induction of a subset of genes in the rat pineal gland.

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Basal aurora kinase B activity is sufficient for histone H3 phosphorylation in prophase

Biology Open ◽

10.1242/bio.20133079 ◽

2013 ◽

Vol 2 (4) ◽

pp. 379-386 ◽

Cited By ~ 15

Author(s):

L.-T.-T. Le ◽

H.-L. Vu ◽

C.-H. Nguyen ◽

A. Molla

Keyword(s):

Histone H3 ◽

Aurora Kinase ◽

Aurora Kinase B ◽

H3 Phosphorylation ◽

Histone H3 Phosphorylation

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Haspin kinase regulates microtubule-organizing center clustering and stability through Aurora kinase C in mouse oocytes

Journal of Cell Science ◽

10.1242/jcs.189340 ◽

2016 ◽

Vol 129 (19) ◽

pp. 3648-3660 ◽

Cited By ~ 19

Author(s):

Ahmed Z. Balboula ◽

Alexandra L. Nguyen ◽

Amanda S. Gentilello ◽

Suzanne M. Quartuccio ◽

David Drutovic ◽

...

Keyword(s):

Aurora Kinase ◽

Microtubule Organizing Center ◽

Mouse Oocytes ◽

Kinase C ◽

Organizing Center

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Dynamics of histone H3 phosphorylation at threonine 3 during meiotic maturation in mouse oocytes

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2015.01.099 ◽

2015 ◽

Vol 458 (2) ◽

pp. 280-286 ◽

Cited By ~ 12

Author(s):

Hyoeun Kang ◽

Yong Seok Park ◽

Dong-Hyung Cho ◽

Jae-Sung Kim ◽

Jeong Su Oh

Keyword(s):

Histone H3 ◽

Meiotic Maturation ◽

Mouse Oocytes ◽

H3 Phosphorylation ◽

Histone H3 Phosphorylation

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Aurora kinase A is essential for meiosis in mouse oocytes

10.1101/2021.01.08.425851 ◽

2021 ◽

Author(s):

Cecilia S. Blengini ◽

Patricia Ibrahimian ◽

Michaela Vaskovicova ◽

David Drutovic ◽

Petr Solc ◽

...

Keyword(s):

Chromosome Segregation ◽

Aurora Kinase ◽

The Other ◽

Meiotic Spindle ◽

Independent Manner ◽

Aurora Kinase A ◽

Mouse Oocytes ◽

Spindle Poles ◽

Knockout Model ◽

Kinase A

The Aurora protein kinases are well-established regulators of spindle building and chromosome segregation in mitotic and meiotic cells. In mouse oocytes, there is significant Aurora kinase A (AURKA) compensatory abilities when the other Aurora kinase homologs are deleted. Whether the other homologs, AURKB or AURKC can compensate for loss of AURKA is not known. Using a conditional mouse oocyte knockout model, we demonstrate that this compensation is not reciprocal because female oocyte-specific knockout mice are sterile and their oocytes fail to complete meiosis I. In determining the AURKA-specific functions, we demonstrate that its first meiotic requirement is to activate Polo-like kinase 1 at microtubule organizing centers (MTOCs; meiotic spindle poles). This activation induces fragmentation of the MTOCs, a step essential for building a bipolar spindle. The next step that requires AURKA is building the liquid-like spindle domain that involves TACC3. Finally, we find that AURKA is also required for anaphase I onset to trigger cohesin cleavage in an APC/C independent manner. We conclude that AURKA has multiple functions essential to completing MI that are distinct from AURKB and AURKC.

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