SMRT-mediated co-shuttling enables export of class IIa HDACs independent of their CaM kinase phosphorylation sites

The Class IIa histone deacetylases (HDAC)4 and HDAC5 play a role in neuronal survival and behavioral adaptation in the CNS. Phosphorylation at 2/3 N-terminal sites promote their nuclear export. We investigated whether non-canonical signaling routes to Class IIa HDAC export exist because of their ass...

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Detalhes bibliográficos
Autores: Soriano Zaragoza, Francesc X. (Francesc Xavier), Chawla, S., Skehel, P., Hardingham, Giles E.
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2013
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/60796
Acesso em linha:https://hdl.handle.net/2445/60796
Access Level:acceso abierto
Palavra-chave:Neurobiologia
Cicle cel·lular
Proteïnes
Enzims
Malalties neurodegeneratives
Neurobiology
Cell cycle
Proteins
Enzymes
Neurodegenerative Diseases
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spelling SMRT-mediated co-shuttling enables export of class IIa HDACs independent of their CaM kinase phosphorylation sitesSoriano Zaragoza, Francesc X. (Francesc Xavier)Chawla, S.Skehel, P.Hardingham, Giles E.NeurobiologiaCicle cel·lularProteïnesEnzimsMalalties neurodegenerativesNeurobiologyCell cycleProteinsEnzymesNeurodegenerative DiseasesThe Class IIa histone deacetylases (HDAC)4 and HDAC5 play a role in neuronal survival and behavioral adaptation in the CNS. Phosphorylation at 2/3 N-terminal sites promote their nuclear export. We investigated whether non-canonical signaling routes to Class IIa HDAC export exist because of their association with the co-repressor Silencing Mediator Of Retinoic And Thyroid Hormone Receptors (SMRT). We found that, while HDAC5 and HDAC4 mutants lacking their N-terminal phosphorylation sites (HDAC4(MUT), HDAC5(MUT)) are constitutively nuclear, co-expression with SMRT renders them exportable by signals that trigger SMRT export, such as synaptic activity, HDAC inhibition, and Brain Derived Neurotrophic Factor (BDNF) signaling. We found that SMRT's repression domain 3 (RD3) is critical for co-shuttling of HDAC5(MUT), consistent with the role for this domain in Class IIa HDAC association. In the context of BDNF signaling, we found that HDAC5(WT), which was more cytoplasmic than HDAC5(MUT), accumulated in the nucleus after BDNF treatment. However, co-expression of SMRT blocked BDNF-induced HDAC5(WT) import in a RD3-dependent manner. In effect, SMRT-mediated HDAC5(WT) export was opposing the BDNF-induced HDAC5 nuclear accumulation observed in SMRT's absence. Thus, SMRT's presence may render Class IIa HDACs exportable by a wider range of signals than those which simplyWiley2014201420132014info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion28 p.application/pdfhttps://hdl.handle.net/2445/60796Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: http://dx.doi.org/10.1111/jnc.12058Journal of Neurochemistry, 2013, vol. 124, num. 1, p. 26-35http://dx.doi.org/10.1111/jnc.12058(c) International Society for Neurochemistry, 2013info:eu-repo/semantics/openAccessoai:recercat.cat:2445/607962026-05-29T05:05:01Z
dc.title.none.fl_str_mv SMRT-mediated co-shuttling enables export of class IIa HDACs independent of their CaM kinase phosphorylation sites
title SMRT-mediated co-shuttling enables export of class IIa HDACs independent of their CaM kinase phosphorylation sites
spellingShingle SMRT-mediated co-shuttling enables export of class IIa HDACs independent of their CaM kinase phosphorylation sites
Soriano Zaragoza, Francesc X. (Francesc Xavier)
Neurobiologia
Cicle cel·lular
Proteïnes
Enzims
Malalties neurodegeneratives
Neurobiology
Cell cycle
Proteins
Enzymes
Neurodegenerative Diseases
title_short SMRT-mediated co-shuttling enables export of class IIa HDACs independent of their CaM kinase phosphorylation sites
title_full SMRT-mediated co-shuttling enables export of class IIa HDACs independent of their CaM kinase phosphorylation sites
title_fullStr SMRT-mediated co-shuttling enables export of class IIa HDACs independent of their CaM kinase phosphorylation sites
title_full_unstemmed SMRT-mediated co-shuttling enables export of class IIa HDACs independent of their CaM kinase phosphorylation sites
title_sort SMRT-mediated co-shuttling enables export of class IIa HDACs independent of their CaM kinase phosphorylation sites
dc.creator.none.fl_str_mv Soriano Zaragoza, Francesc X. (Francesc Xavier)
Chawla, S.
Skehel, P.
Hardingham, Giles E.
author Soriano Zaragoza, Francesc X. (Francesc Xavier)
author_facet Soriano Zaragoza, Francesc X. (Francesc Xavier)
Chawla, S.
Skehel, P.
Hardingham, Giles E.
author_role author
author2 Chawla, S.
Skehel, P.
Hardingham, Giles E.
author2_role author
author
author
dc.subject.none.fl_str_mv Neurobiologia
Cicle cel·lular
Proteïnes
Enzims
Malalties neurodegeneratives
Neurobiology
Cell cycle
Proteins
Enzymes
Neurodegenerative Diseases
topic Neurobiologia
Cicle cel·lular
Proteïnes
Enzims
Malalties neurodegeneratives
Neurobiology
Cell cycle
Proteins
Enzymes
Neurodegenerative Diseases
description The Class IIa histone deacetylases (HDAC)4 and HDAC5 play a role in neuronal survival and behavioral adaptation in the CNS. Phosphorylation at 2/3 N-terminal sites promote their nuclear export. We investigated whether non-canonical signaling routes to Class IIa HDAC export exist because of their association with the co-repressor Silencing Mediator Of Retinoic And Thyroid Hormone Receptors (SMRT). We found that, while HDAC5 and HDAC4 mutants lacking their N-terminal phosphorylation sites (HDAC4(MUT), HDAC5(MUT)) are constitutively nuclear, co-expression with SMRT renders them exportable by signals that trigger SMRT export, such as synaptic activity, HDAC inhibition, and Brain Derived Neurotrophic Factor (BDNF) signaling. We found that SMRT's repression domain 3 (RD3) is critical for co-shuttling of HDAC5(MUT), consistent with the role for this domain in Class IIa HDAC association. In the context of BDNF signaling, we found that HDAC5(WT), which was more cytoplasmic than HDAC5(MUT), accumulated in the nucleus after BDNF treatment. However, co-expression of SMRT blocked BDNF-induced HDAC5(WT) import in a RD3-dependent manner. In effect, SMRT-mediated HDAC5(WT) export was opposing the BDNF-induced HDAC5 nuclear accumulation observed in SMRT's absence. Thus, SMRT's presence may render Class IIa HDACs exportable by a wider range of signals than those which simply
publishDate 2013
dc.date.none.fl_str_mv 2013
2014
2014
2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/60796
url https://hdl.handle.net/2445/60796
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: http://dx.doi.org/10.1111/jnc.12058
Journal of Neurochemistry, 2013, vol. 124, num. 1, p. 26-35
http://dx.doi.org/10.1111/jnc.12058
dc.rights.none.fl_str_mv (c) International Society for Neurochemistry, 2013
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) International Society for Neurochemistry, 2013
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 28 p.
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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