scholarly journals Drosophila Aurora A kinase is required to localize D-TACC to centrosomes and to regulate astral microtubules

2002 ◽  
Vol 156 (3) ◽  
pp. 437-451 ◽  
Author(s):  
Régis Giet ◽  
Doris McLean ◽  
Simon Descamps ◽  
Michael J. Lee ◽  
Jordan W. Raff ◽  
...  
Keyword(s):  
Coiled Coil ◽  
Aurora Kinase ◽  
The Other ◽  
S2 Cells ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Spindle Poles

Disruption of the function of the A-type Aurora kinase of Drosophila by mutation or RNAi leads to a reduction in the length of astral microtubules in syncytial embryos, larval neuroblasts, and cultured S2 cells. In neuroblasts, it can also lead to loss of an organized centrosome and its associated aster from one of the spindle poles, whereas the centrosome at the other pole has multiple centrioles. When centrosomes are present at the poles of aurA mutants or aurA RNAi spindles, they retain many antigens but are missing the Drosophila counterpart of mammalian transforming acidic coiled coil (TACC) proteins, D-TACC. We show that a subpopulation of the total Aurora A is present in a complex with D-TACC, which is a substrate for the kinase. We propose that one of the functions of Aurora A kinase is to direct centrosomal organization such that D-TACC complexed to the MSPS/XMAP215 microtubule-associated protein may be recruited, and thus modulate the behavior of astral microtubules.

scholarly journals Interaction of Aurora-A and centrosomin at the microtubule-nucleating site in Drosophila and mammalian cells

2003 ◽  
Vol 162 (5) ◽  
pp. 757-764 ◽  
Author(s):  
Yasuhiko Terada ◽  
Yumi Uetake ◽  
Ryoko Kuriyama
Keyword(s):  
Mammalian Cells ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Mitotic Spindles ◽  
Microtubule Nucleation ◽  
Microtubule Organization ◽  
Centrosomal Protein ◽  
Spindle Poles

A mitosis-specific Aurora-A kinase has been implicated in microtubule organization and spindle assembly in diverse organisms. However, exactly how Aurora-A controls the microtubule nucleation onto centrosomes is unknown. Here, we show that Aurora-A specifically binds to the COOH-terminal domain of a Drosophila centrosomal protein, centrosomin (CNN), which has been shown to be important for assembly of mitotic spindles and spindle poles. Aurora-A and CNN are mutually dependent for localization at spindle poles, which is required for proper targeting of γ-tubulin and other centrosomal components to the centrosome. The NH2-terminal half of CNN interacts with γ-tubulin, and induces cytoplasmic foci that can initiate microtubule nucleation in vivo and in vitro in both Drosophila and mammalian cells. These results suggest that Aurora-A regulates centrosome assembly by controlling the CNN's ability to targeting and/or anchoring γ-tubulin to the centrosome and organizing microtubule-nucleating sites via its interaction with the COOH-terminal sequence of CNN.

scholarly journals Transforming acidic coiled-coil 3 and Aurora-A interact in human thyrocytes and their expression is deregulated in thyroid cancer tissues

2007 ◽  
Vol 14 (3) ◽  
pp. 827-837 ◽  
Author(s):  
Salvatore Ulisse ◽  
Enke Baldini ◽  
Matteo Toller ◽  
Jean-Guy Delcros ◽  
Aurélie Guého ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Cancer ◽  
Coiled Coil ◽  
Human Thyroid ◽  
Mrna Levels ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Thyroid Cells ◽  
Cancer Tissues

Aurora-A kinase has recently been shown to be deregulated in thyroid cancer cells and tissues. Among the Aurora-A substrates identified, transforming acidic coiled-coil (TACC3), a member of the TACC family, plays an important role in cell cycle progression and alterations of its expression occur in different cancer tissues. In this study, we demonstrated the expression of the TACC3 gene in normal human thyroid cells (HTU5), and its modulation at both mRNA and protein levels during cell cycle. Its expression was found, with respect to HTU5 cells, unchanged in cells derived from a benign thyroid follicular tumor (HTU42), and significantly reduced in cell lines derived from follicular (FTC-133), papillary (B-CPAP), and anaplastic thyroid carcinomas (CAL-62 and 8305C). Moreover, in 16 differentiated thyroid cancer tissues, TACC3 mRNA levels were found, with respect to normal matched tissues, reduced by twofold in 56% of cases and increased by twofold in 44% of cases. In the same tissues, a correlation between the expression of the TACC3 and Aurora-A mRNAs was observed. TACC3 and Aurora-A interact in vivo in thyroid cells and both proteins localized onto the mitotic structure of thyroid cells. Finally, TACC3 localization on spindle microtubule was no more observed following the inhibition of Aurora kinase activity by VX-680. We propose that Aurora-A and TACC3 interaction is important to control the mitotic spindle organization required for proper chromosome segregation.

scholarly journals Coordination of adjacent domains mediates TACC3–ch-TOG–clathrin assembly and mitotic spindle binding

2013 ◽  
Vol 202 (3) ◽  
pp. 463-478 ◽  
Author(s):  
Fiona E. Hood ◽  
Samantha J. Williams ◽  
Selena G. Burgess ◽  
Mark W. Richards ◽  
Daniel Roth ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Coiled Coil ◽  
Spindle Assembly ◽  
The Other ◽  
Cross Linking ◽  
Aurora A ◽  
Dileucine Motif ◽  
Mitotic Spindle Assembly ◽  
Interaction Surface ◽  
Overexpressed Gene

Acomplex of transforming acidic coiled-coil protein 3 (TACC3), colonic and hepatic tumor overexpressed gene (ch-TOG), and clathrin has been implicated in mitotic spindle assembly and in the stabilization of kinetochore fibers by cross-linking microtubules. It is unclear how this complex binds microtubules and how the proteins in the complex interact with one another. TACC3 and clathrin have each been proposed to be the spindle recruitment factor. We have mapped the interactions within the complex and show that TACC3 and clathrin were interdependent for spindle recruitment, having to interact in order for either to be recruited to the spindle. The N-terminal domain of clathrin and the TACC domain of TACC3 in tandem made a microtubule interaction surface, coordinated by TACC3–clathrin binding. A dileucine motif and Aurora A–phosphorylated serine 558 on TACC3 bound to the “ankle” of clathrin. The other interaction within the complex involved a stutter in the TACC3 coiled-coil and a proposed novel sixth TOG domain in ch-TOG, which was required for microtubule localization of ch-TOG but not TACC3–clathrin.

scholarly journals TACC3-ch-TOG track the growing tips of microtubules independently of clathrin and Aurora-A phosphorylation

2014 ◽  
Author(s):  
Cristina Gutiérrez-Caballero ◽  
Selena G Burgess ◽  
Richard Bayliss ◽  
Stephen J Royle
Keyword(s):  
Coiled Coil ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Post Translational Modification ◽  
Centrosomal Protein ◽  
Open Questions ◽  
Binding Surface ◽  
Evolutionarily Conserved ◽  
Dividing Cells ◽  
Overexpressed Gene

The interaction between TACC3 (transforming acidic coiled coil protein 3) and the microtubule polymerase ch-TOG (colonic, hepatic tumor overexpressed gene) is evolutionarily conserved. Loading of TACC3–ch-TOG onto mitotic spindle microtubules requires the phosphorylation of TACC3 by Aurora-A kinase and the subsequent interaction of TACC3 with clathrin to form a microtubule-binding surface. Recent work indicates that TACC3 can track the plus-ends of microtubules and modulate microtubule dynamics in non-dividing cells via its interaction with ch-TOG. Whether there is a pool of TACC3–ch-TOG that is independent of clathrin in human cells, and what is the function of this pool, are open questions. Here, we describe the molecular interaction between TACC3 and ch-TOG that permits TACC3 recruitment to the plus-ends of microtubules. This TACC3–ch-TOG pool is independent of EB1, EB3, Aurora-A phosphorylation and binding to clathrin. We also describe the distinct combinatorial subcellular pools of TACC3, ch-TOG and clathrin. TACC3 is often described as a centrosomal protein, but we show that there is no significant population of TACC3 at centrosomes. The delineation of distinct protein pools reveals a simplified view of how these proteins are organized and controlled by post-translational modification.

scholarly journals Mio depletion links mTOR regulation to Aurora A and Plk1 activation at mitotic centrosomes

2015 ◽  
Vol 210 (1) ◽  
pp. 45-62 ◽  
Author(s):  
Melpomeni Platani ◽  
Laura Trinkle-Mulcahy ◽  
Michael Porter ◽  
A. Arockia Jeyaprakash ◽  
William C. Earnshaw
Keyword(s):  
Mitotic Spindle ◽  
Critical Role ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Spindle Formation ◽  
Major Function ◽  
Mitotic Kinases ◽  
Spindle Poles

Coordination of cell growth and proliferation in response to nutrient supply is mediated by mammalian target of rapamycin (mTOR) signaling. In this study, we report that Mio, a highly conserved member of the SEACAT/GATOR2 complex necessary for the activation of mTORC1 kinase, plays a critical role in mitotic spindle formation and subsequent chromosome segregation by regulating the proper concentration of active key mitotic kinases Plk1 and Aurora A at centrosomes and spindle poles. Mio-depleted cells showed reduced activation of Plk1 and Aurora A kinase at spindle poles and an impaired localization of MCAK and HURP, two key regulators of mitotic spindle formation and known substrates of Aurora A kinase, resulting in spindle assembly and cytokinesis defects. Our results indicate that a major function of Mio in mitosis is to regulate the activation/deactivation of Plk1 and Aurora A, possibly by linking them to mTOR signaling in a pathway to promote faithful mitotic progression.

scholarly journals Aurora A site specific TACC3 phosphorylation regulates astral microtubule assembly by stabilizing γ-tubulin ring complex

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Resmi Rajeev ◽  
Puja Singh ◽  
Ananya Asmita ◽  
Ushma Anand ◽  
Tapas K. Manna
Keyword(s):  
Molecular Mechanisms ◽  
Coiled Coil ◽  
Time Lapse ◽  
Microtubule Assembly ◽  
Aurora A ◽  
Site Specific ◽  
Spindle Poles ◽  
Ring Complex ◽  
Division Axis ◽  
A Site

Abstract Background Astral microtubules emanating from the mitotic centrosomes play pivotal roles in defining cell division axis and tissue morphogenesis. Previous studies have demonstrated that human transforming acidic coiled-coil 3 (TACC3), the most conserved TACC family protein, regulates formation of astral microtubules at centrosomes in vertebrate cells by affecting γ-tubulin ring complex (γ-TuRC) assembly. However, the molecular mechanisms underlying such function were not completely understood. Results Here, we show that Aurora A site-specific phosphorylation in TACC3 regulates formation of astral microtubules by stabilizing γ-TuRC assembly in human cells. Mutation of the most conserved Aurora A targeting site, Ser 558 to alanine (S558A) in TACC3 results in robust loss of astral microtubules and disrupts localization of the γ-tubulin ring complex (γ-TuRC) proteins at the spindle poles. Under similar condition, phospho-mimicking S558D mutation retains astral microtubules and the γ-TuRC proteins in a manner similar to control cells expressed with wild type TACC3. Time-lapse imaging reveals that S558A mutation leads to defects in positioning of the spindle-poles and thereby causes delay in metaphase to anaphase transition. Biochemical results determine that the Ser 558- phosphorylated TACC3 interacts with the γ-TuRC proteins and further, S558A mutation impairs the interaction. We further reveal that the mutation affects the assembly of γ-TuRC from the small complex components. Conclusions The results demonstrate that TACC3 phosphorylation stabilizes γ- tubulin ring complex assembly and thereby regulates formation of centrosomal asters. They also implicate a potential role of TACC3 phosphorylation in the functional integrity of centrosomes/spindle poles.

scholarly journals Aurora A promotes chromosome congression by activating the condensin-dependent pool of KIF4A

2019 ◽  
Vol 219 (2) ◽  
Author(s):  
Elena Poser ◽  
Renaud Caous ◽  
Ulrike Gruneberg ◽  
Francis A. Barr
Keyword(s):  
Metaphase Plate ◽  
Aurora Kinase ◽  
Chromosome Condensation ◽  
Aurora B ◽  
Aurora A ◽  
Specific Point ◽  
Aurora Kinases ◽  
Central Spindle ◽  
Spindle Poles ◽  
Chromosome Congression

Aurora kinases create phosphorylation gradients within the spindle during prometaphase and anaphase, thereby locally regulating factors that promote spindle organization, chromosome condensation and movement, and cytokinesis. We show that one such factor is the kinesin KIF4A, which is present along the chromosome axes throughout mitosis and the central spindle in anaphase. These two pools of KIF4A depend on condensin I and PRC1, respectively. Previous work has shown KIF4A is activated by Aurora B at the anaphase central spindle. However, whether or not chromosome-associated KIF4A bound to condensin I is regulated by Aurora kinases remain unclear. To determine the roles of the two different pools of KIF4A, we generated specific point mutants that are unable to interact with either condensin I or PRC1 or are deficient for Aurora kinase regulation. By analyzing these mutants, we show that Aurora A phosphorylates the condensin I–dependent pool of KIF4A and thus actively promotes chromosome congression from the spindle poles to the metaphase plate.

scholarly journals Aurora kinase A is essential for meiosis in mouse oocytes

PLoS Genetics ◽  
2021 ◽  
Vol 17 (4) ◽  
pp. e1009327
Author(s):  
Cecilia S. Blengini ◽  
Patricia Ibrahimian ◽  
Michaela Vaskovicova ◽  
David Drutovic ◽  
Petr Solc ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Aurora Kinase ◽  
The Other ◽  
Meiotic Spindle ◽  
Multiple Functions ◽  
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 AURKA-specific functions, we demonstrate that its first meiotic requirement is to activate Polo-like kinase 1 at acentriolar microtubule organizing centers (aMTOCs; meiotic spindle poles). This activation induces fragmentation of the aMTOCs, a step essential for building a bipolar spindle. We also show that AURKA is required for regulating localization of TACC3, another protein required for spindle building. We conclude that AURKA has multiple functions essential to completing MI that are distinct from AURKB and AURKC.

scholarly journals Dictyostelium Aurora Kinase Has Properties of both Aurora A and Aurora B Kinases

2008 ◽  
Vol 7 (5) ◽  
pp. 894-905 ◽  
Author(s):  
Hui Li ◽  
Qian Chen ◽  
Markus Kaller ◽  
Wolfgang Nellen ◽  
Ralph Gräf ◽  
...  
Keyword(s):  
Myosin Ii ◽  
Aurora Kinase ◽  
Equatorial Region ◽  
Aurora B ◽  
Cleavage Furrow ◽  
Aurora A ◽  
Animal Cells ◽  
Aurora Kinases ◽  
Spindle Poles ◽  
Early Mitosis

ABSTRACT Aurora kinases are highly conserved proteins with important roles in mitosis. Metazoans contain two kinases, Aurora A and B, which contribute distinct functions at the spindle poles and the equatorial region respectively. It is not currently known whether the specialized functions of the two kinases arose after their duplication in animal cells or were already present in their ancestral kinase. We show that Dictyostelium discoideum contains a single Aurora kinase, DdAurora, that displays characteristics of both Aurora A and B. Like Aurora A, DdAurora has an extended N-terminal domain with an A-box sequence and localizes at the spindle poles during early mitosis. Like Aurora B, DdAurora binds to its partner DdINCENP and localizes on centromeres at metaphase, the central spindle during anaphase, and the cleavage furrow at the end of cytokinesis. DdAurora also has several unusual properties. DdAurora remains associated with centromeres in anaphase, and this association does not require an interaction with DdINCENP. DdAurora then localizes at the cleavage furrow, but only at the end of cytokinesis. This localization is dependent on DdINCENP and the motor proteins Kif12 and myosin II. Thus, DdAurora may represent the ancestral kinase that gave rise to the different Aurora kinases in animals and also those in other organisms.

scholarly journals Aurora A promotes chromosome congression by activating the condensin-dependent pool of KIF4A

2019 ◽  
Author(s):  
Elena Poser ◽  
Renaud Caous ◽  
Ulrike Gruneberg ◽  
Francis A. Barr
Keyword(s):  
Metaphase Plate ◽  
Aurora Kinase ◽  
Chromosome Condensation ◽  
Aurora B ◽  
Aurora A ◽  
Specific Point ◽  
Aurora Kinases ◽  
Central Spindle ◽  
Spindle Poles ◽  
Chromosome Congression

AbstractAurora kinases create phosphorylation gradients within the spindle during prometaphase and anaphase. These locally regulate factors that promote spindle organisation, chromosome condensation and movement, and cytokinesis. We show that one such factor is the kinesin KIF4A, which is present along the chromosome axes throughout mitosis and the central spindle in anaphase. These two pools of KIF4A depend on condensin I and PRC1, respectively. Previous work has shown KIF4A is activated by Aurora B at the anaphase central spindle. However, whether or not chromosome-associated KIF4A bound to condensin I is regulated by Aurora kinases remain unclear. To determine the roles of the two different pools of KIF4A, we generated specific point mutants that are unable to interact with either condensin I or PRC1, or are deficient for Aurora kinase regulation. By analysing these mutants, we show that Aurora kinases phosphorylate the condensin I dependent pool of KIF4A and thus actively promote chromosome congression from the spindle poles to the metaphase plate.

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