scholarly journals Excess TPX2 Interferes with Microtubule Disassembly and Nuclei Reformation at Mitotic Exit

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 374 ◽  
Author(s):  
Francesco D. Naso ◽  
Valentina Sterbini ◽  
Elena Crecca ◽  
Italia A. Asteriti ◽  
Alessandra D. Russo ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Spindle Assembly ◽  
Transformed Cells ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Truncated Form ◽  
Daughter Cells ◽  
Lamin B1 ◽  
Mitotic Spindle Assembly ◽  
Nuclear Reconstitution

The microtubule-associated protein TPX2 is a key mitotic regulator that contributes through distinct pathways to spindle assembly. A well-characterised function of TPX2 is the activation, stabilisation and spindle localisation of the Aurora-A kinase. High levels of TPX2 are reported in tumours and the effects of its overexpression have been investigated in cancer cell lines, while little is known in non-transformed cells. Here we studied TPX2 overexpression in hTERT RPE-1 cells, using either the full length TPX2 or a truncated form unable to bind Aurora-A, to identify effects that are dependent—or independent—on its interaction with the kinase. We observe significant defects in mitotic spindle assembly and progression through mitosis that are more severe when overexpressed TPX2 is able to interact with Aurora-A. Furthermore, we describe a peculiar, and Aurora-A-interaction-independent, phenotype in telophase cells, with aberrantly stable microtubules interfering with nuclear reconstitution and the assembly of a continuous lamin B1 network, resulting in daughter cells displaying doughnut-shaped nuclei. Our results using non-transformed cells thus reveal a previously uncharacterised consequence of abnormally high TPX2 levels on the correct microtubule cytoskeleton remodelling and G1 nuclei reformation, at the mitosis-to-interphase transition.

scholarly journals Aurora A is involved in central spindle assembly through phosphorylation of Ser 19 in P150Glued

2013 ◽  
Vol 201 (1) ◽  
pp. 65-79 ◽  
Author(s):  
David Reboutier ◽  
Marie-Bérengère Troadec ◽  
Jean-Yves Cremet ◽  
Lucie Chauvin ◽  
Vincent Guen ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Spindle Assembly ◽  
Chemical Genetics ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Central Spindle ◽  
Mitotic Spindle Assembly ◽  
In Cells

Knowledge of Aurora A kinase functions is limited to premetaphase events, particularly centrosome maturation, G2/M transition, and mitotic spindle assembly. The involvement of Aurora A in events after metaphase has only been suggested because appropriate experiments are technically difficult. We report here the design of the first human Aurora A kinase (as-AurA) engineered by chemical genetics techniques. This kinase is fully functional biochemically and in cells, and is rapidly and specifically inhibited by the ATP analogue 1-Naphthyl-PP1 (1-Na-PP1). By treating cells exclusively expressing the as-AurA with 1-Na-PP1, we discovered that Aurora A is required for central spindle assembly in anaphase through phosphorylation of Ser 19 of P150Glued. This paper thus describes a new Aurora A function that takes place after the metaphase-to-anaphase transition and a new powerful tool to search for and study new Aurora A functions.

scholarly journals Spatial regulation of Aurora A activity during mitotic spindle assembly requires RHAMM to correctly localize TPX2

Cell Cycle ◽  
2014 ◽  
Vol 13 (14) ◽  
pp. 2248-2261 ◽  
Author(s):  
Helen Chen ◽  
Pooja Mohan ◽  
Jihong Jiang ◽  
Oksana Nemirovsky ◽  
Daniel He ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Spindle Assembly ◽  
Aurora A ◽  
Spatial Regulation ◽  
Mitotic Spindle Assembly

scholarly journals Phase separation of BuGZ promotes Aurora A activation and spindle assembly

2017 ◽  
Vol 217 (1) ◽  
pp. 09-10 ◽  
Author(s):  
Jeffrey B. Woodruff
Keyword(s):  
Phase Separation ◽  
Mitotic Spindle ◽  
Matrix Protein ◽  
Spindle Assembly ◽  
Aurora A ◽  
Spindle Matrix ◽  
Cell Biol ◽  
Mitotic Spindle Assembly

The spindle matrix has been proposed to facilitate mitotic spindle assembly. In this issue, Huang et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201706103) show that the spindle matrix protein BuGZ is sufficient to form micron-scale compartments that recruit and activate Aurora A, a critical kinase for spindle assembly.

scholarly journals AIBp regulates mitotic entry and mitotic spindle assembly by controlling activation of both Aurora-A and Plk1

Cell Cycle ◽  
2015 ◽  
Vol 14 (17) ◽  
pp. 2764-2776 ◽  
Author(s):  
Chia-Hua Chou ◽  
Joon-Khim Loh ◽  
Ming-Chang Yang ◽  
Ching-Chih Lin ◽  
Ming-Chang Hong ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Spindle Assembly ◽  
Aurora A ◽  
Mitotic Entry ◽  
Mitotic Spindle Assembly

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 Targeted disruption of Aurora A causes abnormal mitotic spindle assembly, chromosome misalignment and embryonic lethality

Oncogene ◽  
2008 ◽  
Vol 27 (29) ◽  
pp. 4122-4127 ◽  
Author(s):  
K Sasai ◽  
J M Parant ◽  
M E Brandt ◽  
J Carter ◽  
H P Adams ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Spindle Assembly ◽  
Embryonic Lethality ◽  
Aurora A ◽  
Targeted Disruption ◽  
Mitotic Spindle Assembly

scholarly journals Aurora-A-Dependent Control of TACC3 Influences the Rate of Mitotic Spindle Assembly

PLoS Genetics ◽  
2015 ◽  
Vol 11 (7) ◽  
pp. e1005345 ◽  
Author(s):  
Selena G. Burgess ◽  
Isabel Peset ◽  
Nimesh Joseph ◽  
Tommaso Cavazza ◽  
Isabelle Vernos ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Spindle Assembly ◽  
Aurora A ◽  
Mitotic Spindle Assembly

scholarly journals Aurora A contributes to p150glued phosphorylation and function during mitosis

2010 ◽  
Vol 189 (4) ◽  
pp. 651-659 ◽  
Author(s):  
Pierre Romé ◽  
Emilie Montembault ◽  
Nathalie Franck ◽  
Aude Pascal ◽  
David M. Glover ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Spindle Assembly ◽  
Spindle Pole ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Microtubule Binding ◽  
Microtubule Binding Domain ◽  
Spindle Microtubules ◽  
And Function

Aurora A is a spindle pole–associated protein kinase required for mitotic spindle assembly and chromosome segregation. In this study, we show that Drosophila melanogaster aurora A phosphorylates the dynactin subunit p150glued on sites required for its association with the mitotic spindle. Dynactin strongly accumulates on microtubules during prophase but disappears as soon as the nuclear envelope breaks down, suggesting that its spindle localization is tightly regulated. If aurora A's function is compromised, dynactin and dynein become enriched on mitotic spindle microtubules. Phosphorylation sites are localized within the conserved microtubule-binding domain (MBD) of the p150glued. Although wild-type p150glued binds weakly to spindle microtubules, a variant that can no longer be phosphorylated by aurora A remains associated with spindle microtubules and fails to rescue depletion of endogenous p150glued. Our results suggest that aurora A kinase participates in vivo to the phosphoregulation of the p150glued MBD to limit the microtubule binding of the dynein–dynactin complex and thus regulates spindle assembly.

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