Excess TPX2 Interferes with Microtubule Disassembly and Nuclei Reformation at Mitotic Exit
Francesco D. Naso,
Valentina Sterbini,
Elena Crecca,
Italia A. Asteriti,
Alessandra D. Russo,
Maria Giubettini,
Enrico Cundari,
Catherine Lindon,
Alessandro Rosa,
Giulia Guarguaglini
Affiliations
Francesco D. Naso
Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy
Valentina Sterbini
Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy
Elena Crecca
Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy
Italia A. Asteriti
Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy
Alessandra D. Russo
Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy
Maria Giubettini
CrestOptics S.p.A., Via di Torre Rossa 66, 00165 Rome, Italy
Enrico Cundari
Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy
Catherine Lindon
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK
Alessandro Rosa
Center for Life Nano Science, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy
Giulia Guarguaglini
Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy
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.
