10.3390/cells9020374 Excess TPX2 Interferes with Microtubule Disassembly and Nuclei Reformation at Mitotic Exit Naso Francesco D. Dr. Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy francesco.naso@uniroma1.it Sterbini Valentina Dr. Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy v.sterbini@hsantalucia.it Crecca Elena Dr. 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@uniroma1.it Asteriti Italia A. Dr. Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy lia.asteriti@uniroma1.it Russo Alessandra D. Dr. Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy alessandrarusso19@gmail.com Giubettini Maria Dr. CrestOptics S.p.A., Via di Torre Rossa 66, 00165 Rome, Italy Center for Life Nano Science, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy giubettini@crestopt.com Cundari Enrico Dr. Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy enrico.cundari@uniroma1.it Lindon Catherine Dr. Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK acl34@cam.ac.uk http://orcid.org/0000-0001-9999-7223 Rosa Alessandro Dr. Center for Life Nano Science, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy Department of Biology and Biotechnology “C. Darwin”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy alessandro.rosa@uniroma1.it Guarguaglini Giulia Dr. Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy giulia.guarguaglini@uniroma1.it 06 02 2020 9 2 29 01 2020 e374 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. Associazione Italiana per la Ricerca sul Cancro IG-17390 Royal Society IES/RE/170195 Regione Lazio 85-2017-15348 © 1996-2020 MDPI (Basel, Switzerland) 2020 This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited TPX2 mitosis spindle nuclear envelope Cells Cells 2073-4409 MDPI