Mutant huntingtin affects endocytosis in striatal cells by altering the binding of AP-2 to membranes

Autores
Borgonovo, Janina Edith; Troncoso, Mariana Elizabeth; Lucas, José J.; Sosa Escudero, Miguel Angel
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Clathrin-mediated endocytosis plays an important role in the maintenance of neuronal integrity in the synaptic terminals. Here we studied the effect of anomalous polyglutamine expansion in huntingtin on the interaction of coat proteins with membranes, in areas of mouse brain or in cultured striatal cells. We observed that this anomaly induces a redistribution of AP-2, but not other coat proteins, from the membrane to the cytosol in the striatum, and in the cultured striatal cells. It was also noted that huntingtin associates with AP-2, and that this association decreases due to the mutation in huntingtin. This decreased receptor-mediated endocytosis, measured by the internalization of transferrin in the mutated cells. It was also confirmed that huntingtin mutation made the cells more vulnerable to the action of quinolinic acid, with an increasing degradation of the AP-2 alpha subunits. On the basis of these results, we conclude that abnormal polyglutamine expansion in huntingtin affects clathrin-mediated endocytosis, and may be one of the pathogenic mechanisms of neurodegeneration.
Fil: Borgonovo, Janina Edith. Consejo Nacional de Investigaciones Cientficas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza "Dr. M. Burgos"; Argentina
Fil: Troncoso, Mariana Elizabeth. Consejo Nacional de Investigaciones Cientficas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza "Dr. M. Burgos"; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Lucas, José J.. Universidad Autónoma de Madrid. Consejo superior de Investigaciones Científicas. Centro de Biología Molecular "Severo Ochoa"; España
Fil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Cientficas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza "Dr. M. Burgos"; Argentina
Materia
Endocytosis
Clathrin Coated Vesicles
Neurodegeneration
Huntingtin
Huntington'S Disease
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/10077
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mutant huntingtin affects endocytosis in striatal cells by altering the binding of AP-2 to membranesBorgonovo, Janina EdithTroncoso, Mariana ElizabethLucas, José J.Sosa Escudero, Miguel AngelEndocytosisClathrin Coated VesiclesNeurodegenerationHuntingtinHuntington'S Diseasehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Clathrin-mediated endocytosis plays an important role in the maintenance of neuronal integrity in the synaptic terminals. Here we studied the effect of anomalous polyglutamine expansion in huntingtin on the interaction of coat proteins with membranes, in areas of mouse brain or in cultured striatal cells. We observed that this anomaly induces a redistribution of AP-2, but not other coat proteins, from the membrane to the cytosol in the striatum, and in the cultured striatal cells. It was also noted that huntingtin associates with AP-2, and that this association decreases due to the mutation in huntingtin. This decreased receptor-mediated endocytosis, measured by the internalization of transferrin in the mutated cells. It was also confirmed that huntingtin mutation made the cells more vulnerable to the action of quinolinic acid, with an increasing degradation of the AP-2 alpha subunits. On the basis of these results, we conclude that abnormal polyglutamine expansion in huntingtin affects clathrin-mediated endocytosis, and may be one of the pathogenic mechanisms of neurodegeneration.Fil: Borgonovo, Janina Edith. Consejo Nacional de Investigaciones Cientficas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza "Dr. M. Burgos"; ArgentinaFil: Troncoso, Mariana Elizabeth. Consejo Nacional de Investigaciones Cientficas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza "Dr. M. Burgos"; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Lucas, José J.. Universidad Autónoma de Madrid. Consejo superior de Investigaciones Científicas. Centro de Biología Molecular "Severo Ochoa"; EspañaFil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Cientficas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza "Dr. M. Burgos"; ArgentinaElsevier2013-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/10077Borgonovo, Janina Edith; Troncoso, Mariana Elizabeth; Lucas, José J.; Sosa Escudero, Miguel Angel; Mutant huntingtin affects endocytosis in striatal cells by altering the binding of AP-2 to membranes; Elsevier; Experimental Neurology; 241; 3-2013; 75-830014-4886enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014488612004426info:eu-repo/semantics/altIdentifier/doi/10.1016/j.expneurol.2012.11.025info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T11:02:28Zoai:ri.conicet.gov.ar:11336/10077instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-17 11:02:28.691CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mutant huntingtin affects endocytosis in striatal cells by altering the binding of AP-2 to membranes
title Mutant huntingtin affects endocytosis in striatal cells by altering the binding of AP-2 to membranes
spellingShingle Mutant huntingtin affects endocytosis in striatal cells by altering the binding of AP-2 to membranes
Borgonovo, Janina Edith
Endocytosis
Clathrin Coated Vesicles
Neurodegeneration
Huntingtin
Huntington'S Disease
title_short Mutant huntingtin affects endocytosis in striatal cells by altering the binding of AP-2 to membranes
title_full Mutant huntingtin affects endocytosis in striatal cells by altering the binding of AP-2 to membranes
title_fullStr Mutant huntingtin affects endocytosis in striatal cells by altering the binding of AP-2 to membranes
title_full_unstemmed Mutant huntingtin affects endocytosis in striatal cells by altering the binding of AP-2 to membranes
title_sort Mutant huntingtin affects endocytosis in striatal cells by altering the binding of AP-2 to membranes
dc.creator.none.fl_str_mv Borgonovo, Janina Edith
Troncoso, Mariana Elizabeth
Lucas, José J.
Sosa Escudero, Miguel Angel
author Borgonovo, Janina Edith
author_facet Borgonovo, Janina Edith
Troncoso, Mariana Elizabeth
Lucas, José J.
Sosa Escudero, Miguel Angel
author_role author
author2 Troncoso, Mariana Elizabeth
Lucas, José J.
Sosa Escudero, Miguel Angel
author2_role author
author
author
dc.subject.none.fl_str_mv Endocytosis
Clathrin Coated Vesicles
Neurodegeneration
Huntingtin
Huntington'S Disease
topic Endocytosis
Clathrin Coated Vesicles
Neurodegeneration
Huntingtin
Huntington'S Disease
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Clathrin-mediated endocytosis plays an important role in the maintenance of neuronal integrity in the synaptic terminals. Here we studied the effect of anomalous polyglutamine expansion in huntingtin on the interaction of coat proteins with membranes, in areas of mouse brain or in cultured striatal cells. We observed that this anomaly induces a redistribution of AP-2, but not other coat proteins, from the membrane to the cytosol in the striatum, and in the cultured striatal cells. It was also noted that huntingtin associates with AP-2, and that this association decreases due to the mutation in huntingtin. This decreased receptor-mediated endocytosis, measured by the internalization of transferrin in the mutated cells. It was also confirmed that huntingtin mutation made the cells more vulnerable to the action of quinolinic acid, with an increasing degradation of the AP-2 alpha subunits. On the basis of these results, we conclude that abnormal polyglutamine expansion in huntingtin affects clathrin-mediated endocytosis, and may be one of the pathogenic mechanisms of neurodegeneration.
Fil: Borgonovo, Janina Edith. Consejo Nacional de Investigaciones Cientficas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza "Dr. M. Burgos"; Argentina
Fil: Troncoso, Mariana Elizabeth. Consejo Nacional de Investigaciones Cientficas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza "Dr. M. Burgos"; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Lucas, José J.. Universidad Autónoma de Madrid. Consejo superior de Investigaciones Científicas. Centro de Biología Molecular "Severo Ochoa"; España
Fil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Cientficas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza "Dr. M. Burgos"; Argentina
description Clathrin-mediated endocytosis plays an important role in the maintenance of neuronal integrity in the synaptic terminals. Here we studied the effect of anomalous polyglutamine expansion in huntingtin on the interaction of coat proteins with membranes, in areas of mouse brain or in cultured striatal cells. We observed that this anomaly induces a redistribution of AP-2, but not other coat proteins, from the membrane to the cytosol in the striatum, and in the cultured striatal cells. It was also noted that huntingtin associates with AP-2, and that this association decreases due to the mutation in huntingtin. This decreased receptor-mediated endocytosis, measured by the internalization of transferrin in the mutated cells. It was also confirmed that huntingtin mutation made the cells more vulnerable to the action of quinolinic acid, with an increasing degradation of the AP-2 alpha subunits. On the basis of these results, we conclude that abnormal polyglutamine expansion in huntingtin affects clathrin-mediated endocytosis, and may be one of the pathogenic mechanisms of neurodegeneration.
publishDate 2013
dc.date.none.fl_str_mv 2013-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/10077
Borgonovo, Janina Edith; Troncoso, Mariana Elizabeth; Lucas, José J.; Sosa Escudero, Miguel Angel; Mutant huntingtin affects endocytosis in striatal cells by altering the binding of AP-2 to membranes; Elsevier; Experimental Neurology; 241; 3-2013; 75-83
0014-4886
url http://hdl.handle.net/11336/10077
identifier_str_mv Borgonovo, Janina Edith; Troncoso, Mariana Elizabeth; Lucas, José J.; Sosa Escudero, Miguel Angel; Mutant huntingtin affects endocytosis in striatal cells by altering the binding of AP-2 to membranes; Elsevier; Experimental Neurology; 241; 3-2013; 75-83
0014-4886
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014488612004426
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.expneurol.2012.11.025
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.001348

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