Homeostasis of the astrocytic glutamate transporter GLT-1 is altered in mouse models of Lafora disease

10 páginas, 6 figuras

Detalles Bibliográficos
Autores: Muñoz-Ballester, Carmen, Berthier, Arnaud, Viana, Rosa, Sanz, Pascual
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/131032
Acceso en línea:http://hdl.handle.net/10261/131032
Access Level:acceso abierto
Palabra clave:Lafora disease
Epilepsy
Glutamate transport
Ubiquitination
Endocytosis
Protein recycling
EAAT2
GLT-1
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spelling Homeostasis of the astrocytic glutamate transporter GLT-1 is altered in mouse models of Lafora diseaseMuñoz-Ballester, CarmenBerthier, ArnaudViana, RosaSanz, PascualLafora diseaseEpilepsyGlutamate transportUbiquitinationEndocytosisProtein recyclingEAAT2GLT-110 páginas, 6 figurasLafora disease (LD, OMIM 254780) is a fatal rare disorder characterized by epilepsy and neurodegeneration. Although in recent years a lot of information has been gained on the molecular basis of the neurodegeneration that accompanies LD, the molecular basis of epilepsy is poorly understood. Here, we present evidence indicating that the homeostasis of glutamate transporter GLT-1 (EAAT2) is compromised in mouse models of LD. Our results indicate that primary astrocytes from LD mice have reduced capacity of glutamate transport, probably because they present a reduction in the levels of the glutamate transporter at the plasma membrane. On the other hand, the overexpression in cellular models of laforin and malin, the two proteins related to LD, results in an accumulation of GLT-1 (EAAT2) at the plasma membrane and in a severe reduction of the ubiquitination of the transporter. All these results suggest that the laforin/malin complex slows down the endocytic recycling of the GLT-1 (EAAT2) transporter. Since, defects in the function of this transporter lead to excitotoxicity and epilepsy, we suggest that the epilepsy that accompanies LD could be due, at least in part, to deficiencies in the function of the GLT-1 (EAAT2) transporter.This work was supported by grants from the Spanish Ministry of Education and Science SAF2014-54604-C3-1-R, an ACCI2012 action from CIBERER, a grant from the Alicia Koplowitz Foundation (2015) and a grant from Generalitat Valenciana (PrometeoII/2014/029). A.B. held a postdoctoral fellowship from the Program “Junta para la Ampliación de Estudios” (JAE-Doc) co-funded by the European Social Fund (ESF). C.M-B holds a FPU fellowship from the Spanish Ministry of Education, Culture and Sports.Peer reviewedElsevierMinisterio de Educación y Ciencia (España)Centro de Investigación Biomédica en Red Enfermedades Raras (España)Fundación Alicia KoplowitzGeneralitat ValencianaEuropean Science FoundationConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201620162016info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/131032reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1016/j.bbadis.2016.03.008Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1310322026-05-22T06:33:51Z
dc.title.none.fl_str_mv Homeostasis of the astrocytic glutamate transporter GLT-1 is altered in mouse models of Lafora disease
title Homeostasis of the astrocytic glutamate transporter GLT-1 is altered in mouse models of Lafora disease
spellingShingle Homeostasis of the astrocytic glutamate transporter GLT-1 is altered in mouse models of Lafora disease
Muñoz-Ballester, Carmen
Lafora disease
Epilepsy
Glutamate transport
Ubiquitination
Endocytosis
Protein recycling
EAAT2
GLT-1
title_short Homeostasis of the astrocytic glutamate transporter GLT-1 is altered in mouse models of Lafora disease
title_full Homeostasis of the astrocytic glutamate transporter GLT-1 is altered in mouse models of Lafora disease
title_fullStr Homeostasis of the astrocytic glutamate transporter GLT-1 is altered in mouse models of Lafora disease
title_full_unstemmed Homeostasis of the astrocytic glutamate transporter GLT-1 is altered in mouse models of Lafora disease
title_sort Homeostasis of the astrocytic glutamate transporter GLT-1 is altered in mouse models of Lafora disease
dc.creator.none.fl_str_mv Muñoz-Ballester, Carmen
Berthier, Arnaud
Viana, Rosa
Sanz, Pascual
author Muñoz-Ballester, Carmen
author_facet Muñoz-Ballester, Carmen
Berthier, Arnaud
Viana, Rosa
Sanz, Pascual
author_role author
author2 Berthier, Arnaud
Viana, Rosa
Sanz, Pascual
author2_role author
author
author
dc.contributor.none.fl_str_mv Ministerio de Educación y Ciencia (España)
Centro de Investigación Biomédica en Red Enfermedades Raras (España)
Fundación Alicia Koplowitz
Generalitat Valenciana
European Science Foundation
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Lafora disease
Epilepsy
Glutamate transport
Ubiquitination
Endocytosis
Protein recycling
EAAT2
GLT-1
topic Lafora disease
Epilepsy
Glutamate transport
Ubiquitination
Endocytosis
Protein recycling
EAAT2
GLT-1
description 10 páginas, 6 figuras
publishDate 2016
dc.date.none.fl_str_mv 2016
2016
2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/131032
url http://hdl.handle.net/10261/131032
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1016/j.bbadis.2016.03.008
Sí
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
_version_ 1869406506619764736
score 15,811543

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