In Xenopus egg extracts, Tpx2 is required for the Ran-GTP (601179)-dependent assembly of microtubules around chromosomes. Gruss et al. (2002) found that interfering with the function of human TPX2 in HeLa cells caused defects in microtubule organization during mitosis.
General function
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Cellular localization
Cytoskeleton
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Ovarian function
Oogenesis
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Expression regulated by
FSH
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FSH regulates mRNA translation in mouse oocytes and promotes developmental competence. Franciosi F et al. (2015) A major challenge in assisted reproductive technology is to develop conditions for in vitro oocyte maturation yielding high-quality eggs. Efforts are underway to assess whether known hormonal and local factors play a role in oocyte developmental competence and to identify the molecular mechanism involved. Here, we have tested the hypothesis that FSH improves oocyte developmental competence by regulating the translational program in the oocyte. Accumulation of oocyte proteins (TPX2 and IL7) associated with improved oocyte quality is increased when cumulus/oocyte complexes are incubated with FSH. This increase is due to enhanced translation of the corresponding mRNAs, as indicated by microinjection of constructs where the 3`UTR of the Tpx2 or Il7 transcripts is fused to the luciferase reporter. A transient activation of the PI3K/AKT cascade in the oocyte preceded the increase in translation. When the EGF receptor is down-regulated in follicular cells, the FSH-induced rate of maternal mRNA translation and AKT activation were lost, demonstrating that the effects of FSH are indirect and require EGFR-signaling in the somatic compartment. Using Pten(fl/fl):Zp3cre oocytes where AKT is constitutively activated, translation of reporters was increased and was no longer sensitive to FSH stimulation. More importantly, the oocytes lacking Pten showed increased developmental competence even when cultured in the absence of FSH or growth factors. Thus, we demonstrate that FSH intersects with the follicular EGF-network to activate the PI3K/AKT cascade in the oocyte to control translation and developmental competence. These findings provide a molecular rationale for the use of FSH to improve egg quality.//////////////////
Phosphorylation of TPX2 by Plx1 enhances activation of Aurora A. Eckerdt F et al. Entry into mitosis requires the activation of mitotic kinases, including Aurora A and Polo-like kinase 1 (Plk1). Increased levels of these kinases are frequently found associated with human cancers, and therefore it is imperative to understand the processes leading to their activation. We demonstrate that TPX2, but neither Ajuba nor Inhibitor-2, can activate Aurora A directly. Moreover, Plx1 can induce Aurora A T-loop phosphorylation indirectly in vivo during oocyte maturation. We identify Ser204 in TPX2 as a Plx1 phosphorylation site. Mutating Ser204 to alanine decreases activation of Aurora A, whereas a phosphomimetic Asp mutant exhibits enhanced activating ability. Finally, we show that phosphorylation of TPX2 with Plx1 increases its ability to activate Aurora A. Taken together, our data indicate that Plx1 promotes activation of Aurora A, most likely through TPX2. In light of the current literature, we propose a model in which Plx1 and Aurora A activate each other in a positive feedback loop.
Ovarian localization
Oocyte
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Meiotic regulation of TPX2 protein levels governs cell cycle progression in mouse oocytes. Brunet S et al. Formation of female gametes requires acentriolar spindle assembly during meiosis. Mitotic spindles organize from centrosomes and via local activation of the RanGTPase on chromosomes. Vertebrate oocytes present a RanGTP gradient centred on chromatin at all stages of meiotic maturation. However, this gradient is dispensable for assembly of the first meiotic spindle. To understand this meiosis I peculiarity, we studied TPX2, a Ran target, in mouse oocytes. Strikingly, TPX2 activity is controlled at the protein level through its accumulation from meiosis I to II. By RNAi depletion and live imaging, we show that TPX2 is required for spindle assembly via two distinct functions. It controls microtubule assembly and spindle pole integrity via the phosphorylation of TACC3, a regulator of MTOCs activity. We show that meiotic spindle formation in vivo depends on the regulation of at least a target of Ran, TPX2, rather than on the regulation of the RanGTP gradient itself.