The role of NEDD1 phosphorylation by Aurora A in chromosomal microtubule nucleation and spindle function

Chromatin directs de novo microtubule (MT) nucleation in dividing cells by generating a gradient of GTP-bound Ran protein (RanGTP) that controls the activity of a number of spindle assembly factors (SAFs). It is now well established that these MTs are essential for the assembly of a functional bipol...

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Detalles Bibliográficos
Autores: Pinyol, Roser, Scrofani, Jacopo, 1984-, Vernos, Isabelle, 1959-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/23504
Acceso en línea:http://hdl.handle.net/10230/23504
http://dx.doi.org/10.1016/j.cub.2012.11.046
Access Level:acceso abierto
Palabra clave:Microtúbuls
Proteïnes
Cicle cel·lular
id ES_b8c266d4b030ea19c7889f7c6368b607
oai_identifier_str oai:repositori.upf.edu:10230/23504
network_acronym_str ES
network_name_str España
repository_id_str
spelling The role of NEDD1 phosphorylation by Aurora A in chromosomal microtubule nucleation and spindle functionPinyol, RoserScrofani, Jacopo, 1984-Vernos, Isabelle, 1959-MicrotúbulsProteïnesCicle cel·lularChromatin directs de novo microtubule (MT) nucleation in dividing cells by generating a gradient of GTP-bound Ran protein (RanGTP) that controls the activity of a number of spindle assembly factors (SAFs). It is now well established that these MTs are essential for the assembly of a functional bipolar spindle. Although it has been shown that RanGTP-dependent MT nucleation requires γ-tubulin and a number of RanGTP-regulated proteins, the mechanism involved is still poorly understood. We previously showed that the mitotic kinase Aurora A, which is activated in a RanGTP-dependent manner in mitotic cells, has a role in this pathway. Here we show that Aurora A interacts with and phosphorylates the γTURC adaptor protein NEDD1 at a single residue, Ser405. Ser405 phosphorylation is not required for centrosomal MT nucleation but is critical for MT nucleation in the vicinity of the chromosomes in mitotic cells. Moreover, it is essential for RanGTP aster formation and chromatin-driven MT assembly in Xenopus egg extracts. Our data suggest that one important function of Aurora A in mitotic cells is to promote MT nucleation around the chromatin by phosphorylating NEDD1, and thereby to promote functional spindle assembly.This work was supported by grants Consolider-Ingenio 2010 CENTROSOME_3D CSD2006-00023 and/nBFU2009-10202. J.S. is supported by a PhD student fellowship from La CaixaElsevier201520152013info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/23504http://dx.doi.org/10.1016/j.cub.2012.11.046reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésCurrent Biology. 2013 Jan 21;23(2):143-9info:eu-repo/grantAgreement/ES/2PN/CSD2006-00023info:eu-repo/grantAgreement/ES/3PN/BFU2009-10202This is the published version of an article http://dx.doi.org/10.1016/j.cub.2012.11.046 that appeared in the journal Current Biology [© Elsevier Inc ]. It is published in an Open Archive under an Elsevier user license. Details of this licence are available here: http://www.elsevier.com/about/open-access/open-access-policies/oa-license-policy/elsevier-user-licenseinfo:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/235042026-06-12T07:21:37Z
dc.title.none.fl_str_mv The role of NEDD1 phosphorylation by Aurora A in chromosomal microtubule nucleation and spindle function
title The role of NEDD1 phosphorylation by Aurora A in chromosomal microtubule nucleation and spindle function
spellingShingle The role of NEDD1 phosphorylation by Aurora A in chromosomal microtubule nucleation and spindle function
Pinyol, Roser
Microtúbuls
Proteïnes
Cicle cel·lular
title_short The role of NEDD1 phosphorylation by Aurora A in chromosomal microtubule nucleation and spindle function
title_full The role of NEDD1 phosphorylation by Aurora A in chromosomal microtubule nucleation and spindle function
title_fullStr The role of NEDD1 phosphorylation by Aurora A in chromosomal microtubule nucleation and spindle function
title_full_unstemmed The role of NEDD1 phosphorylation by Aurora A in chromosomal microtubule nucleation and spindle function
title_sort The role of NEDD1 phosphorylation by Aurora A in chromosomal microtubule nucleation and spindle function
dc.creator.none.fl_str_mv Pinyol, Roser
Scrofani, Jacopo, 1984-
Vernos, Isabelle, 1959-
author Pinyol, Roser
author_facet Pinyol, Roser
Scrofani, Jacopo, 1984-
Vernos, Isabelle, 1959-
author_role author
author2 Scrofani, Jacopo, 1984-
Vernos, Isabelle, 1959-
author2_role author
author
dc.subject.none.fl_str_mv Microtúbuls
Proteïnes
Cicle cel·lular
topic Microtúbuls
Proteïnes
Cicle cel·lular
description Chromatin directs de novo microtubule (MT) nucleation in dividing cells by generating a gradient of GTP-bound Ran protein (RanGTP) that controls the activity of a number of spindle assembly factors (SAFs). It is now well established that these MTs are essential for the assembly of a functional bipolar spindle. Although it has been shown that RanGTP-dependent MT nucleation requires γ-tubulin and a number of RanGTP-regulated proteins, the mechanism involved is still poorly understood. We previously showed that the mitotic kinase Aurora A, which is activated in a RanGTP-dependent manner in mitotic cells, has a role in this pathway. Here we show that Aurora A interacts with and phosphorylates the γTURC adaptor protein NEDD1 at a single residue, Ser405. Ser405 phosphorylation is not required for centrosomal MT nucleation but is critical for MT nucleation in the vicinity of the chromosomes in mitotic cells. Moreover, it is essential for RanGTP aster formation and chromatin-driven MT assembly in Xenopus egg extracts. Our data suggest that one important function of Aurora A in mitotic cells is to promote MT nucleation around the chromatin by phosphorylating NEDD1, and thereby to promote functional spindle assembly.
publishDate 2013
dc.date.none.fl_str_mv 2013
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/23504
http://dx.doi.org/10.1016/j.cub.2012.11.046
url http://hdl.handle.net/10230/23504
http://dx.doi.org/10.1016/j.cub.2012.11.046
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Current Biology. 2013 Jan 21;23(2):143-9
info:eu-repo/grantAgreement/ES/2PN/CSD2006-00023
info:eu-repo/grantAgreement/ES/3PN/BFU2009-10202
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812455

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