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 ◽  
...  

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.

Cell Cycle ◽  
2014 ◽  
Vol 13 (14) ◽  
pp. 2248-2261 ◽  
Author(s):  
Helen Chen ◽  
Pooja Mohan ◽  
Jihong Jiang ◽  
Oksana Nemirovsky ◽  
Daniel He ◽  
...  

2017 ◽  
Vol 217 (1) ◽  
pp. 09-10 ◽  
Author(s):  
Jeffrey B. Woodruff

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.


2002 ◽  
Vol 3 (5) ◽  
pp. 673-684 ◽  
Author(s):  
Danielle R. Hamill ◽  
Aaron F. Severson ◽  
J.Clayton Carter ◽  
Bruce Bowerman

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 ◽  
...  

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 374 ◽  
Author(s):  
Francesco D. Naso ◽  
Valentina Sterbini ◽  
Elena Crecca ◽  
Italia A. Asteriti ◽  
Alessandra D. Russo ◽  
...  

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.


Oncogene ◽  
2008 ◽  
Vol 27 (29) ◽  
pp. 4122-4127 ◽  
Author(s):  
K Sasai ◽  
J M Parant ◽  
M E Brandt ◽  
J Carter ◽  
H P Adams ◽  
...  

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

2005 ◽  
Vol 16 (6) ◽  
pp. 2836-2847 ◽  
Author(s):  
Lori L. O'Brien ◽  
Alison J. Albee ◽  
Lingling Liu ◽  
Wei Tao ◽  
Pawel Dobrzyn ◽  
...  

Maskin is the Xenopus homolog of the transforming acidic coiled coil (TACC)-family of microtubule and centrosome-interacting proteins. Members of this family share a ∼200 amino acid coiled coil motif at their C-termini, but have only limited homology outside of this domain. In all species examined thus far, perturbations of TACC proteins lead to disruptions of cell cycle progression and/or embryonic lethality. In Drosophila, Caenorhabditis elegans, and humans, these disruptions have been attributed to mitotic spindle assembly defects, and the TACC proteins in these organisms are thought to function as structural components of the spindle. In contrast, cell division failure in early Xenopus embryo blastomeres has been attributed to a role of maskin in regulating the translation of, among others, cyclin B1 mRNA. In this study, we show that maskin, like other TACC proteins, plays a direct role in mitotic spindle assembly in Xenopus egg extracts and that this role is independent of cyclin B. Maskin immunodepletion and add-back experiments demonstrate that maskin, or a maskin-associated activity, is required for two distinct steps during spindle assembly in Xenopus egg extracts that can be distinguished by their response to “rescue” experiments. Defects in the “early” step, manifested by greatly reduced aster size during early time points in maskin-depleted extracts, can be rescued by readdition of purified full-length maskin. Moreover, defects in this step can also be rescued by addition of only the TACC-domain of maskin. In contrast, defects in the “late” step during spindle assembly, manifested by abnormal spindles at later time points, cannot be rescued by readdition of maskin. We show that maskin interacts with a number of proteins in egg extracts, including XMAP215, a known modulator of microtubule dynamics, and CPEB, a protein that is involved in translational regulation of important cell cycle regulators. Maskin depletion from egg extracts results in compromised microtubule asters and spindles and the mislocalization of XMAP215, but CPEB localization is unaffected. Together, these data suggest that in addition to its previously reported role as a translational regulator, maskin is also important for mitotic spindle assembly.


Sign in / Sign up

Export Citation Format

Share Document