CDKL5 localizes at the centrosome and midbody and is required for faithful cell division

Abstract The cyclin-dependent kinase-like 5 (CDKL5) gene has been associated with rare neurodevelopmental disorders characterized by the early onset of seizures and intellectual disability. The CDKL5 protein is widely expressed in most tissues and cells with both nuclear and cytoplasmic localization...

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Autores principales:	Isabella Barbiero, Davide Valente, Chetan Chandola, Fiorenza Magi, Anna Bergo, Laura Monteonofrio, Marco Tramarin, Maria Fazzari, Silvia Soddu, Nicoletta Landsberger, Cinzia Rinaldo, Charlotte Kilstrup-Nielsen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fbcbc72f52974687a41eb08fed046097
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spelling	oai:doaj.org-article:fbcbc72f52974687a41eb08fed0460972021-12-02T11:52:55ZCDKL5 localizes at the centrosome and midbody and is required for faithful cell division10.1038/s41598-017-05875-z2045-2322https://doaj.org/article/fbcbc72f52974687a41eb08fed0460972017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05875-zhttps://doaj.org/toc/2045-2322Abstract The cyclin-dependent kinase-like 5 (CDKL5) gene has been associated with rare neurodevelopmental disorders characterized by the early onset of seizures and intellectual disability. The CDKL5 protein is widely expressed in most tissues and cells with both nuclear and cytoplasmic localization. In post-mitotic neurons CDKL5 is mainly involved in dendritic arborization, axon outgrowth, and spine formation while in proliferating cells its function is still largely unknown. Here, we report that CDKL5 localizes at the centrosome and at the midbody in proliferating cells. Acute inactivation of CDKL5 by RNA interference (RNAi) leads to multipolar spindle formation, cytokinesis failure and centrosome accumulation. At the molecular level, we observed that, among the several midbody components we analyzed, midbodies of CDKL5-depleted cells were devoid of HIPK2 and its cytokinesis target, the extrachromosomal histone H2B phosphorylated at S14. Of relevance, expression of the phosphomimetic mutant H2B-S14D, which is capable of overcoming cytokinesis failure in HIPK2-defective cells, was sufficient to rescue spindle multipolarity in CDKL5-depleted cells. Taken together, these results highlight a hitherto unknown role of CDKL5 in regulating faithful cell division by guaranteeing proper HIPK2/H2B functions at the midbody.Isabella BarbieroDavide ValenteChetan ChandolaFiorenza MagiAnna BergoLaura MonteonofrioMarco TramarinMaria FazzariSilvia SodduNicoletta LandsbergerCinzia RinaldoCharlotte Kilstrup-NielsenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Isabella Barbiero Davide Valente Chetan Chandola Fiorenza Magi Anna Bergo Laura Monteonofrio Marco Tramarin Maria Fazzari Silvia Soddu Nicoletta Landsberger Cinzia Rinaldo Charlotte Kilstrup-Nielsen CDKL5 localizes at the centrosome and midbody and is required for faithful cell division
description	Abstract The cyclin-dependent kinase-like 5 (CDKL5) gene has been associated with rare neurodevelopmental disorders characterized by the early onset of seizures and intellectual disability. The CDKL5 protein is widely expressed in most tissues and cells with both nuclear and cytoplasmic localization. In post-mitotic neurons CDKL5 is mainly involved in dendritic arborization, axon outgrowth, and spine formation while in proliferating cells its function is still largely unknown. Here, we report that CDKL5 localizes at the centrosome and at the midbody in proliferating cells. Acute inactivation of CDKL5 by RNA interference (RNAi) leads to multipolar spindle formation, cytokinesis failure and centrosome accumulation. At the molecular level, we observed that, among the several midbody components we analyzed, midbodies of CDKL5-depleted cells were devoid of HIPK2 and its cytokinesis target, the extrachromosomal histone H2B phosphorylated at S14. Of relevance, expression of the phosphomimetic mutant H2B-S14D, which is capable of overcoming cytokinesis failure in HIPK2-defective cells, was sufficient to rescue spindle multipolarity in CDKL5-depleted cells. Taken together, these results highlight a hitherto unknown role of CDKL5 in regulating faithful cell division by guaranteeing proper HIPK2/H2B functions at the midbody.
format	article
author	Isabella Barbiero Davide Valente Chetan Chandola Fiorenza Magi Anna Bergo Laura Monteonofrio Marco Tramarin Maria Fazzari Silvia Soddu Nicoletta Landsberger Cinzia Rinaldo Charlotte Kilstrup-Nielsen
author_facet	Isabella Barbiero Davide Valente Chetan Chandola Fiorenza Magi Anna Bergo Laura Monteonofrio Marco Tramarin Maria Fazzari Silvia Soddu Nicoletta Landsberger Cinzia Rinaldo Charlotte Kilstrup-Nielsen
author_sort	Isabella Barbiero
title	CDKL5 localizes at the centrosome and midbody and is required for faithful cell division
title_short	CDKL5 localizes at the centrosome and midbody and is required for faithful cell division
title_full	CDKL5 localizes at the centrosome and midbody and is required for faithful cell division
title_fullStr	CDKL5 localizes at the centrosome and midbody and is required for faithful cell division
title_full_unstemmed	CDKL5 localizes at the centrosome and midbody and is required for faithful cell division
title_sort	cdkl5 localizes at the centrosome and midbody and is required for faithful cell division
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/fbcbc72f52974687a41eb08fed046097
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CDKL5 localizes at the centrosome and midbody and is required for faithful cell division

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