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Microtubule-Associated Proteins with Regulatory Functions by Day and Pathological Potency at Night
Open AccessArticle

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

1
Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy
2
CrestOptics S.p.A., Via di Torre Rossa 66, 00165 Rome, Italy
3
Center for Life Nano Science, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy
4
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK
5
Department of Biology and Biotechnology “C. Darwin”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
*
Author to whom correspondence should be addressed.
Present address: Experimental Neuropsychobiology Laboratory, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.
Present address: Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.
§
Present address: Centro Analisi Pasteur S.r.l., 93017 San Cataldo (CL), Italy.
Cells 2020, 9(2), 374; https://doi.org/10.3390/cells9020374
Received: 20 December 2019 / Revised: 24 January 2020 / Accepted: 29 January 2020 / Published: 6 February 2020
(This article belongs to the Special Issue The Microtubule Cytoskeleton in Chromosome Segregation and Beyond)
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. View Full-Text
Keywords: TPX2; mitosis; spindle; nuclear envelope TPX2; mitosis; spindle; nuclear envelope
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Naso, F.D.; Sterbini, V.; Crecca, E.; Asteriti, I.A.; Russo, A.D.; Giubettini, M.; Cundari, E.; Lindon, C.; Rosa, A.; Guarguaglini, G. Excess TPX2 Interferes with Microtubule Disassembly and Nuclei Reformation at Mitotic Exit. Cells 2020, 9, 374.

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