Hsp90 activity is necessary to acquire a proper neuronal polarization

Chaperones are critical for the folding and regulation of a wide array of cellular proteins. Heat Shock Proteins (Hsps) are the most representative group of chaperones. Hsp90 represents up to 1-2% of soluble protein. Although the Hsp90 role is being studied in neurodegenerative diseases, its role in...

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Detalles Bibliográficos
Autores: Benítez, María J., Sánchez-Ponce, Diana, Garrido Jurado, Juan José, Wandosell, Francisco
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/146649
Acceso en línea:http://hdl.handle.net/10261/146649
Access Level:acceso abierto
Palabra clave:Neuronal chaperons Hsp90 Axon Neuronal polarity PI3K Akt pathway
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spelling Hsp90 activity is necessary to acquire a proper neuronal polarizationBenítez, María J.Sánchez-Ponce, DianaGarrido Jurado, Juan JoséWandosell, FranciscoNeuronal chaperons Hsp90 Axon Neuronal polarity PI3K Akt pathwayChaperones are critical for the folding and regulation of a wide array of cellular proteins. Heat Shock Proteins (Hsps) are the most representative group of chaperones. Hsp90 represents up to 1-2% of soluble protein. Although the Hsp90 role is being studied in neurodegenerative diseases, its role in neuronal differentiation remains mostly unknown. Since neuronal polarity mechanisms depend on local stability and degradation, we asked whether Hsp90 could be a regulator of axonal polarity and growth. Thus, we studied the role of Hsp90 activity in a well established model of cultured hippocampal neurons using an Hsp90 specific inhibitor, 17-AAG. Our present data shows that Hsp90 inhibition at different developmental stages disturbs neuronal polarity formation or axonal elongation. Hsp90 inhibition during the first 3. h in culture promotes multiple axon morphology, while this inhibition after 3. h slows down axonal elongation. Hsp90 inhibition was accompanied by decreased Akt and GSK3 expression, as well as, a reduced Akt activity. In parallel, we detected an alteration of kinesin-1 subcellular distribution. Moreover, these effects were seconded by changes in Hsp70/Hsc70 subcellular localization that seem to compensate the lack of Hsp90 activity. In conclusion, our data strongly suggests that Hsp90 activity is necessary to control the expression, activity or location of specific kinases and motor proteins during the axon specification and axon elongation processes. Even more, our data demonstrate the existence of a >time-window> for axon specification in this model of cultured neurons after which the inhibition of Hsp90 only affects axonal elongation mechanisms. © 2013 Elsevier B.V.Peer ReviewedElsevier2017201720142017info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/146649reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglésinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1466492026-05-22T06:33:51Z
dc.title.none.fl_str_mv Hsp90 activity is necessary to acquire a proper neuronal polarization
title Hsp90 activity is necessary to acquire a proper neuronal polarization
spellingShingle Hsp90 activity is necessary to acquire a proper neuronal polarization
Benítez, María J.
Neuronal chaperons Hsp90 Axon Neuronal polarity PI3K Akt pathway
title_short Hsp90 activity is necessary to acquire a proper neuronal polarization
title_full Hsp90 activity is necessary to acquire a proper neuronal polarization
title_fullStr Hsp90 activity is necessary to acquire a proper neuronal polarization
title_full_unstemmed Hsp90 activity is necessary to acquire a proper neuronal polarization
title_sort Hsp90 activity is necessary to acquire a proper neuronal polarization
dc.creator.none.fl_str_mv Benítez, María J.
Sánchez-Ponce, Diana
Garrido Jurado, Juan José
Wandosell, Francisco
author Benítez, María J.
author_facet Benítez, María J.
Sánchez-Ponce, Diana
Garrido Jurado, Juan José
Wandosell, Francisco
author_role author
author2 Sánchez-Ponce, Diana
Garrido Jurado, Juan José
Wandosell, Francisco
author2_role author
author
author
dc.subject.none.fl_str_mv Neuronal chaperons Hsp90 Axon Neuronal polarity PI3K Akt pathway
topic Neuronal chaperons Hsp90 Axon Neuronal polarity PI3K Akt pathway
description Chaperones are critical for the folding and regulation of a wide array of cellular proteins. Heat Shock Proteins (Hsps) are the most representative group of chaperones. Hsp90 represents up to 1-2% of soluble protein. Although the Hsp90 role is being studied in neurodegenerative diseases, its role in neuronal differentiation remains mostly unknown. Since neuronal polarity mechanisms depend on local stability and degradation, we asked whether Hsp90 could be a regulator of axonal polarity and growth. Thus, we studied the role of Hsp90 activity in a well established model of cultured hippocampal neurons using an Hsp90 specific inhibitor, 17-AAG. Our present data shows that Hsp90 inhibition at different developmental stages disturbs neuronal polarity formation or axonal elongation. Hsp90 inhibition during the first 3. h in culture promotes multiple axon morphology, while this inhibition after 3. h slows down axonal elongation. Hsp90 inhibition was accompanied by decreased Akt and GSK3 expression, as well as, a reduced Akt activity. In parallel, we detected an alteration of kinesin-1 subcellular distribution. Moreover, these effects were seconded by changes in Hsp70/Hsc70 subcellular localization that seem to compensate the lack of Hsp90 activity. In conclusion, our data strongly suggests that Hsp90 activity is necessary to control the expression, activity or location of specific kinases and motor proteins during the axon specification and axon elongation processes. Even more, our data demonstrate the existence of a >time-window> for axon specification in this model of cultured neurons after which the inhibition of Hsp90 only affects axonal elongation mechanisms. © 2013 Elsevier B.V.
publishDate 2014
dc.date.none.fl_str_mv 2014
2017
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/146649
url http://hdl.handle.net/10261/146649
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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