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 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 Overexpression of the Centrosomal Protein Aurora-A Kinase is Associated with Poor Prognosis in Epithelial Ovarian Cancer Patients

2007 ◽  
Vol 13 (14) ◽  
pp. 4098-4104 ◽  
Author(s):  
Charles N. Landen ◽  
Yvonne G. Lin ◽  
Anand Immaneni ◽  
Michael T. Deavers ◽  
William M. Merritt ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Centrosomal Protein

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 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.

Overexpression of the centrosomal protein aurora-A kinase is associated with poor prognosis in epithelial ovarian cancer patients

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 5039-5039 ◽  
Author(s):  
C. N. Landen ◽  
A. Immaneni ◽  
M. T. Deavers ◽  
A. Thornton ◽  
J. Celestino ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Centrosomal Protein

scholarly journals Arpc1b, a centrosomal protein, is both an activator and substrate of Aurora A

2010 ◽  
Vol 190 (1) ◽  
pp. 101-114 ◽  
Author(s):  
Poonam R. Molli ◽  
Da-Qiang Li ◽  
Rozita Bagheri-Yarmand ◽  
Suresh B. Pakala ◽  
Hiroshi Katayama ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Centrosome Amplification ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Independent Manner ◽  
Centrosomal Protein ◽  
Kinase Activation

Here we provide evidence in support of an inherent role for Arpc1b, a component of the Arp2/3 complex, in regulation of mitosis and demonstrate that its depletion inhibits Aurora A activation at the centrosome and impairs the ability of mammalian cells to enter mitosis. We discovered that Arpc1b colocalizes with γ-tubulin at centrosomes and stimulates Aurora A activity. Aurora A phosphorylates Arpc1b on threonine 21, and expression of Arpc1b but not a nonphosphorylatable Arpc1b mutant in mammalian cells leads to Aurora A kinase activation and abnormal centrosome amplification in a Pak1-independent manner. Together, these findings reveal a new function for Arpc1b in centrosomal homeostasis. Arpc1b is both a physiological activator and substrate of Aurora A kinase and these interactions help to maintain mitotic integrity in mammalian cells.

scholarly journals The centrosomal protein Lats2 is a phosphorylation target of Aurora-A kinase

2004 ◽  
Vol 9 (5) ◽  
pp. 383-397 ◽  
Author(s):  
Shingo Toji ◽  
Norikazu Yabuta ◽  
Toshiya Hosomi ◽  
Souichi Nishihara ◽  
Toshiko Kobayashi ◽  
...  
Keyword(s):  
Aurora A Kinase ◽  
Aurora A ◽  
Centrosomal Protein

scholarly journals Clathrin promotes centrosome integrity in early mitosis through stabilization of centrosomal ch-TOG

2012 ◽  
Vol 198 (4) ◽  
pp. 591-605 ◽  
Author(s):  
Amy B. Foraker ◽  
Stéphane M. Camus ◽  
Timothy M. Evans ◽  
Sophia R. Majeed ◽  
Chih-Ying Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Kinase Inhibitor ◽  
Coiled Coil ◽  
S Phase ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Multipolar Spindles ◽  
Associated Proteins ◽  
A Cell ◽  
Spindle Stability

Clathrin depletion by ribonucleic acid interference (RNAi) impairs mitotic spindle stability and cytokinesis. Depletion of several clathrin-associated proteins affects centrosome integrity, suggesting a further cell cycle function for clathrin. In this paper, we report that RNAi depletion of CHC17 (clathrin heavy chain 17) clathrin, but not the CHC22 clathrin isoform, induced centrosome amplification and multipolar spindles. To stage clathrin function within the cell cycle, a cell line expressing SNAP-tagged clathrin light chains was generated. Acute clathrin inactivation by chemical dimerization of the SNAP-tag during S phase caused reduction of both clathrin and ch-TOG (colonic, hepatic tumor overexpressed gene) at metaphase centrosomes, which became fragmented. This was phenocopied by treatment with Aurora A kinase inhibitor, suggesting a centrosomal role for the Aurora A–dependent complex of clathrin, ch-TOG, and TACC3 (transforming acidic coiled-coil protein 3). Clathrin inactivation in S phase also reduced total cellular levels of ch-TOG by metaphase. Live-cell imaging showed dynamic clathrin recruitment during centrosome maturation. Therefore, we propose that clathrin promotes centrosome maturation by stabilizing the microtubule-binding protein ch-TOG, defining a novel role for the clathrin–ch-TOG–TACC3 complex.

Centrosome Aurora A gradient ensures single polarity axis in C. elegans embryos

2020 ◽  
Vol 48 (3) ◽  
pp. 1243-1253 ◽  
Author(s):  
Sukriti Kapoor ◽  
Sachin Kotak
Keyword(s):  
Symmetry Breaking ◽  
Cell Fate ◽  
Cell Cortex ◽  
Axis Formation ◽  
Aurora A Kinase ◽  
Aurora A ◽  
C Elegans ◽  
Cell Embryo ◽  
Polarity Establishment

Cellular asymmetries are vital for generating cell fate diversity during development and in stem cells. In the newly fertilized Caenorhabditis elegans embryo, centrosomes are responsible for polarity establishment, i.e. anterior–posterior body axis formation. The signal for polarity originates from the centrosomes and is transmitted to the cell cortex, where it disassembles the actomyosin network. This event leads to symmetry breaking and the establishment of distinct domains of evolutionarily conserved PAR proteins. However, the identity of an essential component that localizes to the centrosomes and promotes symmetry breaking was unknown. Recent work has uncovered that the loss of Aurora A kinase (AIR-1 in C. elegans and hereafter referred to as Aurora A) in the one-cell embryo disrupts stereotypical actomyosin-based cortical flows that occur at the time of polarity establishment. This misregulation of actomyosin flow dynamics results in the occurrence of two polarity axes. Notably, the role of Aurora A in ensuring a single polarity axis is independent of its well-established function in centrosome maturation. The mechanism by which Aurora A directs symmetry breaking is likely through direct regulation of Rho-dependent contractility. In this mini-review, we will discuss the unconventional role of Aurora A kinase in polarity establishment in C. elegans embryos and propose a refined model of centrosome-dependent symmetry breaking.

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