Homeostasis of the astrocytic glutamate transporter GLT-1 is altered in mouse models of Lafora disease
10 páginas, 6 figuras
| Autores: | , , , |
|---|---|
| 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 |
| id |
ES_3e24c33e6378564381f7e985b3c8666e |
|---|---|
| oai_identifier_str |
oai:digital.csic.es:10261/131032 |
| network_acronym_str |
ES |
| network_name_str |
España |
| spelling |
Homeostasis of the astrocytic glutamate transporter GLT-1 is altered in mouse models of Lafora disease Muñoz-Ballester, Carmen Berthier, Arnaud Viana, Rosa Sanz, Pascual Lafora disease Epilepsy Glutamate transport Ubiquitination Endocytosis Protein recycling EAAT2 GLT-1 10 páginas, 6 figuras Lafora 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 reviewed Elsevier http://hdl.handle.net/10261/131032 |
| 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 |
| 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 |
| topic |
Lafora disease Epilepsy Glutamate transport Ubiquitination Endocytosis Protein recycling EAAT2 GLT-1 |
| topic_facet |
Lafora disease Epilepsy Glutamate transport Ubiquitination Endocytosis Protein recycling EAAT2 GLT-1 |
| description |
10 páginas, 6 figuras |
| publishDate |
2016 |
| format |
article |
| status_str |
acceptedVersion |
| url |
http://hdl.handle.net/10261/131032 |
| eu_rights_str_mv |
openAccess |
| publisher |
Elsevier |
| institution |
Consejo Superior de Investigaciones Científicas (CSIC) |
| collection |
DIGITAL.CSIC. Repositorio Institucional del CSIC |
| reponame_str |
DIGITAL.CSIC. Repositorio Institucional del CSIC |
| instname_str |
Consejo Superior de Investigaciones Científicas (CSIC) |
| _version_ |
1878433691426881536 |
| publishDateSort |
2016 |
| author_browse |
Berthier, Arnaud Muñoz-Ballester, Carmen Sanz, Pascual Viana, Rosa |
| publisherStr |
Elsevier |
| score |
6.9303427 |