Aurora Kinase A Drives MTOC Biogenesis but Does Not Trigger Resumption of Meiosis in Mouse Oocytes Matured In Vivo1

Solc, P; Baran, Vladimı́r; Mayer, Alexandra; Bohmova, Tereza; Panenkova-Havlova, Gabriela; Saskova, Adela; Schultz, Richard M.; Motlı́k, Jan

doi:10.1095/biolreprod.112.101014

Cited by 44 publications

(44 citation statements)

References 66 publications

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“…Additionally, it has been reported that Aurka is a critical regulator of spindle assembly and MTOC biogenesis in mouse oocytes. 25,27,38,39 Aurka localized in the cytoplasm of GV oocytes and accumulated on the spindle poles in MI and MII oocytes; another report had similar findings (Fig. S1C).…”

Section: Bcl2l10 Controls Meiotic Spindle Assembly By Regulating Mtocsupporting

confidence: 71%

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Bcl2l10, a new Tpx2 binding partner, is a master regulator of Aurora kinase A in mouse oocytes

Lee

Kim

et al. 2016

Cell Cycle

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Previously, we demonstrated that Bcl-2-like 10 (Bcl2l10) is associated with meiotic spindle assembly and that the gene that is most strongly down-regulated by Bcl2l10 RNAi is targeting protein for Xklp2 (Tpx2). Tpx2 is a well-known cofactor that controls the activity and localization of Aurora kinase A (Aurka) during mitotic spindle assembly. Therefore, this study was conducted (1) to identify the associations among Bcl2l10, Tpx2, and Aurka and (2) to understand how Bcl2l10 regulates meiotic spindle assembly in mouse oocytes. Bcl2l10, Tpx2, and Aurka co-localized on the meiotic spindles, and Bcl2l10 was present in the same complex with Tpx2. Tpx2 and Aurka expression decreased whereas phospho-Aurka increased in Bcl2l10 RNAi-treated oocytes. Counterbalancing changes in the levels of these 2 activators, Tpx2 and phospho-Aurka, resulted in decreased Aurka catalytic activity after Bcl2l10 RNAi treatment. Bcl2l10 RNAi decreased the expression of microtubule organizing center (MTOC)-related proteins, disturbed MTOC formation and disrupted meiotic spindle assembly. Our data demonstrate that Bcl2l10 is a binding partner of Tpx2 and a new regulator of the complex controlling the organization of microtubules and MTOC biogenesis in meiotic spindle assembly. The discovery of Bcl2l10 as a new effector of Aurka suggests that Bcl2l10 may have diverse functions in mitotic cells.

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Section: Bcl2l10 Controls Meiotic Spindle Assembly By Regulating Mtocsupporting

confidence: 71%

“…Because the auto-phosphorylation of Aurka occurred in the MTOCs of mouse oocytes, 25,27 we co-stained T288-Aurka and Pericentrin. T288-Aurka was not concentrated at the MTOC as indicated by Pericentrin but was dispersed in the cytoplasm of the MIarrested oocytes after Bcl2l10 RNAi (Fig.…”

Section: Bcl2l10 Rnai Disturbed Mtoc Formation In Oocytesmentioning

confidence: 99%

Bcl2l10, a new Tpx2 binding partner, is a master regulator of Aurora kinase A in mouse oocytes

Lee

Kim

et al. 2016

Cell Cycle

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“…Because AURKA localizes to MTOCs (Saskova et al, 2008;Shuda et al, 2009;Solc et al, 2012), and because its inhibition can cause spindle pole instability in mitotic cells , we wondered whether haspin regulates AURKA localization at MTOCs. First, we compared AURKA levels in oocytes fixed at metaphase I by performing immunocytochemistry.…”

Section: Haspin Does Not Regulate Aurka Localization At Mtocsmentioning

confidence: 99%

“…One protein that localizes with the PCM in somatic cells and oocytes is Aurora kinase A (AURKA) (Saskova et al, 2008;Shuda et al, 2009;Solc et al, 2012). In somatic cells (Ma et al, 2011), upon binding a microtubule-binding protein called TPX2, AURKA auto-activates and regulates the building of the bipolar spindle by recruiting other PCM proteins, promoting microtubule nucleation and anti-parallel sliding forces, and maintaining the integrity of astral microtubules with the cortex (Dodson and Bayliss, 2012;Giubettini et al, 2011;Kufer et al, 2002;Li et al, 2008;Scrofani et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…In somatic cells (Ma et al, 2011), upon binding a microtubule-binding protein called TPX2, AURKA auto-activates and regulates the building of the bipolar spindle by recruiting other PCM proteins, promoting microtubule nucleation and anti-parallel sliding forces, and maintaining the integrity of astral microtubules with the cortex (Dodson and Bayliss, 2012;Giubettini et al, 2011;Kufer et al, 2002;Li et al, 2008;Scrofani et al, 2015). In mouse oocytes, overexpression of AURKA increases MTOC numbers prematurely (Saskova et al, 2008;Solc et al, 2012), and its depletion causes disorganized meiosis I spindles (Saskova et al, 2008). Overexpression of TPX2 in mouse oocytes results in multipolar spindles whereas its depletion ablates the spindle (Brunet et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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

Balboula

Nguyen

Gentilello

et al. 2016

Journal of Cell Science

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Meiotic oocytes lack classic centrosomes and, therefore, bipolar spindle assembly depends on clustering of acentriolar microtubuleorganizing centers (MTOCs) into two poles. However, the molecular mechanism regulating MTOC assembly into two poles is not fully understood. The kinase haspin (also known as GSG2) is required to regulate Aurora kinase C (AURKC) localization at chromosomes during meiosis I. Here, we show that inhibition of haspin perturbed MTOC clustering into two poles and the stability of the clustered MTOCs. Furthermore, we show that AURKC localizes to MTOCs in mouse oocytes. Inhibition of haspin perturbed the localization of AURKC at MTOCs, and overexpression of AURKC rescued the MTOC-clustering defects in haspin-inhibited oocytes. Taken together, our data uncover a role for haspin as a regulator of bipolar spindle assembly by regulating AURKC function at acentriolar MTOCs in oocytes.

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TP53BP1 regulates chromosome alignment and spindle bipolarity in mouse oocytes

Jin

Namgoong

2019

Molecular Reproduction Devel

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Meiotic oocytes lack classic centrosomes; therefore, bipolar spindle assembly depends on the clustering of acentriolar microtubule‐organizing centers (MTOCs) into two poles. The bipolar spindle is an essential cellular component that ensures accurate chromosome segregation during anaphase. If the spindle does not form properly, it can result in aneuploidy or cell death. However, the molecular mechanism by which the bipolar spindle is established is not yet fully understood. Tumor suppressor p53‐binding protein 1 (TP53BP1) is known to mediate the DNA damage response. Several recent studies have indicated that TP53BP1 has noncanonical roles in processes, such as spindle formation; however, the role of TP53BP1 in oocyte meiosis is currently unclear. Our results show that TP53BP1 knockdown affects spindle bipolarity and chromatin alignment by altering MTOC stability during oocyte maturation. TP53BP1 was localized in the cytoplasm and displayed an irregular cloud pattern around the spindle/chromosome region. TP53BP1 was also required for the correct localization of MTOCs into the two spindle poles during pro‐meiosis I. TP53BP1 deletion altered the MTOC‐localized Aurora Kinase A. TP53BP1 knockdown caused the microtubules to detach from the kinetochores and increased the rate of aneuploidy. Taken together, our data show that TP53BP1 plays crucial roles in chromosome stability and spindle bipolarity during meiotic maturation.

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Aurora Kinase A Drives MTOC Biogenesis but Does Not Trigger Resumption of Meiosis in Mouse Oocytes Matured In Vivo1

Cited by 44 publications

References 66 publications

Bcl2l10, a new Tpx2 binding partner, is a master regulator of Aurora kinase A in mouse oocytes

Bcl2l10, a new Tpx2 binding partner, is a master regulator of Aurora kinase A in mouse oocytes

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

TP53BP1 regulates chromosome alignment and spindle bipolarity in mouse oocytes

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