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Kinesin-2 Controls the Motility of RAB5 Endosomes and Their Association with the Spindle in Mitosis

RAB5 is a small GTPase that belongs to the wide family of Rab proteins and localizes on early endosomes. In its active GTP-bound form, RAB5 recruits downstream effectors that, in turn, are responsible for distinct aspects of early endosome function, including their movement along microtubules. We pr...

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Detalles Bibliográficos
Autores principales: Pupo, Emanuela, Avanzato, Daniele, Scianna, Marco, Oldani, Amanda, Serini, Guido, Lanzetti, Letizia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163544/
https://www.ncbi.nlm.nih.gov/pubmed/30200238
http://dx.doi.org/10.3390/ijms19092575
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author Pupo, Emanuela
Avanzato, Daniele
Scianna, Marco
Oldani, Amanda
Serini, Guido
Lanzetti, Letizia
author_facet Pupo, Emanuela
Avanzato, Daniele
Scianna, Marco
Oldani, Amanda
Serini, Guido
Lanzetti, Letizia
author_sort Pupo, Emanuela
collection PubMed
description RAB5 is a small GTPase that belongs to the wide family of Rab proteins and localizes on early endosomes. In its active GTP-bound form, RAB5 recruits downstream effectors that, in turn, are responsible for distinct aspects of early endosome function, including their movement along microtubules. We previously reported that, at the onset of mitosis, RAB5positive vesicles cluster around the spindle poles and, during metaphase, move along spindle microtubules. RNAi-mediated depletion of the three RAB5 isoforms delays nuclear envelope breakdown at prophase and severely affects chromosome alignment and segregation. Here we show that depletion of the Kinesin-2 motor complex impairs long-range movement of RAB5 endosomes in interphase cells and prevents localization of these vesicles at the spindle during metaphase. Similarly to the effect caused by RAB5 depletion, functional ablation of Kinesin-2 delays nuclear envelope breakdown resulting in prolonged prophase. Altogether these findings suggest that endosomal transport at the onset of mitosis is required to control timing of nuclear envelope breakdown.
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spelling pubmed-61635442018-10-10 Kinesin-2 Controls the Motility of RAB5 Endosomes and Their Association with the Spindle in Mitosis Pupo, Emanuela Avanzato, Daniele Scianna, Marco Oldani, Amanda Serini, Guido Lanzetti, Letizia Int J Mol Sci Article RAB5 is a small GTPase that belongs to the wide family of Rab proteins and localizes on early endosomes. In its active GTP-bound form, RAB5 recruits downstream effectors that, in turn, are responsible for distinct aspects of early endosome function, including their movement along microtubules. We previously reported that, at the onset of mitosis, RAB5positive vesicles cluster around the spindle poles and, during metaphase, move along spindle microtubules. RNAi-mediated depletion of the three RAB5 isoforms delays nuclear envelope breakdown at prophase and severely affects chromosome alignment and segregation. Here we show that depletion of the Kinesin-2 motor complex impairs long-range movement of RAB5 endosomes in interphase cells and prevents localization of these vesicles at the spindle during metaphase. Similarly to the effect caused by RAB5 depletion, functional ablation of Kinesin-2 delays nuclear envelope breakdown resulting in prolonged prophase. Altogether these findings suggest that endosomal transport at the onset of mitosis is required to control timing of nuclear envelope breakdown. MDPI 2018-08-30 /pmc/articles/PMC6163544/ /pubmed/30200238 http://dx.doi.org/10.3390/ijms19092575 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pupo, Emanuela
Avanzato, Daniele
Scianna, Marco
Oldani, Amanda
Serini, Guido
Lanzetti, Letizia
Kinesin-2 Controls the Motility of RAB5 Endosomes and Their Association with the Spindle in Mitosis
title Kinesin-2 Controls the Motility of RAB5 Endosomes and Their Association with the Spindle in Mitosis
title_full Kinesin-2 Controls the Motility of RAB5 Endosomes and Their Association with the Spindle in Mitosis
title_fullStr Kinesin-2 Controls the Motility of RAB5 Endosomes and Their Association with the Spindle in Mitosis
title_full_unstemmed Kinesin-2 Controls the Motility of RAB5 Endosomes and Their Association with the Spindle in Mitosis
title_short Kinesin-2 Controls the Motility of RAB5 Endosomes and Their Association with the Spindle in Mitosis
title_sort kinesin-2 controls the motility of rab5 endosomes and their association with the spindle in mitosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163544/
https://www.ncbi.nlm.nih.gov/pubmed/30200238
http://dx.doi.org/10.3390/ijms19092575
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