Dynamics of GABABR signaling: influence of cholesterol and aging
- Autores
- Vásquez, Elena; Masone, Diego Fernando; Muñoz, Estela Maris
- Año de publicación
- 2021
- Idioma
- inglés
- Tipo de recurso
- documento de conferencia
- Estado
- versión publicada
- Descripción
- GABA B receptors (GABABRs) are obligatory heterodimers which belong to the superfamily of G protein-coupled receptors (GPCRs). Age-related changes in membrane cholesterol levels modulate membrane fluidity, which in-turn influences GPCRs´ localization and function. We studied the GABABR and also a transmembrane transporter structurally homologous to KCC2. To characterize transient conformational changes over time, molecular dynamics simulations were performed using a neuronal plasma membrane (PM) model. Two different membrane cholesterol levels were evaluated: 45% and 10%, which intend to resemble the composition of adult and aged neuronal PMs, respectively. For experimental verification in both young and aged cerebella, we determined protein expression and distribution, and we assessed whether the two proteins interact with each other in vivo. Techniques were: western blots (WB), co-immunoprecipitation assays, and multiple immunolabeling followed by confocal microscopy. Our results suggest that the expression and spatial distribution of both proteins change as the cerebellum grows older. Based on our in silico analyses, we infer that a G protein-independent interaction does occur. Also, we confirmed that the two proteins are part of the same complex in the cerebellum. As our simulations indicate, we propose that the underlying mechanism implies transient conformational changes, which are highly dependent on cholesterol levels and are therefore affected by the aging process.
Fil: Vásquez, Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Masone, Diego Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Muñoz, Estela Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
XXXIV Annual Meeting of Argentine Society for Research in Neurosciences
Villa Carlos Paz
Argentina
Argentine Society for Research in Neurosciences - Materia
-
GABA
GABA RECEPTORS
AGEING
CHOLESTEROL - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/202358
Ver los metadatos del registro completo
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Dynamics of GABABR signaling: influence of cholesterol and agingVásquez, ElenaMasone, Diego FernandoMuñoz, Estela MarisGABAGABA RECEPTORSAGEINGCHOLESTEROLhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1GABA B receptors (GABABRs) are obligatory heterodimers which belong to the superfamily of G protein-coupled receptors (GPCRs). Age-related changes in membrane cholesterol levels modulate membrane fluidity, which in-turn influences GPCRs´ localization and function. We studied the GABABR and also a transmembrane transporter structurally homologous to KCC2. To characterize transient conformational changes over time, molecular dynamics simulations were performed using a neuronal plasma membrane (PM) model. Two different membrane cholesterol levels were evaluated: 45% and 10%, which intend to resemble the composition of adult and aged neuronal PMs, respectively. For experimental verification in both young and aged cerebella, we determined protein expression and distribution, and we assessed whether the two proteins interact with each other in vivo. Techniques were: western blots (WB), co-immunoprecipitation assays, and multiple immunolabeling followed by confocal microscopy. Our results suggest that the expression and spatial distribution of both proteins change as the cerebellum grows older. Based on our in silico analyses, we infer that a G protein-independent interaction does occur. Also, we confirmed that the two proteins are part of the same complex in the cerebellum. As our simulations indicate, we propose that the underlying mechanism implies transient conformational changes, which are highly dependent on cholesterol levels and are therefore affected by the aging process.Fil: Vásquez, Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Masone, Diego Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Muñoz, Estela Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaXXXIV Annual Meeting of Argentine Society for Research in NeurosciencesVilla Carlos PazArgentinaArgentine Society for Research in NeurosciencesSAGE Publications2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/202358Dynamics of GABABR signaling: influence of cholesterol and aging; XXXIV Annual Meeting of Argentine Society for Research in Neurosciences ; Villa Carlos Paz; Argentina; 2019; 23-231759-0914CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.sagepub.com/doi/10.1177/1759091420979851info:eu-repo/semantics/altIdentifier/doi/10.1177/1759091420979851Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:38:39Zoai:ri.conicet.gov.ar:11336/202358instacron: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:34982025-09-29 09:38:39.943CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Dynamics of GABABR signaling: influence of cholesterol and aging |
title |
Dynamics of GABABR signaling: influence of cholesterol and aging |
spellingShingle |
Dynamics of GABABR signaling: influence of cholesterol and aging Vásquez, Elena GABA GABA RECEPTORS AGEING CHOLESTEROL |
title_short |
Dynamics of GABABR signaling: influence of cholesterol and aging |
title_full |
Dynamics of GABABR signaling: influence of cholesterol and aging |
title_fullStr |
Dynamics of GABABR signaling: influence of cholesterol and aging |
title_full_unstemmed |
Dynamics of GABABR signaling: influence of cholesterol and aging |
title_sort |
Dynamics of GABABR signaling: influence of cholesterol and aging |
dc.creator.none.fl_str_mv |
Vásquez, Elena Masone, Diego Fernando Muñoz, Estela Maris |
author |
Vásquez, Elena |
author_facet |
Vásquez, Elena Masone, Diego Fernando Muñoz, Estela Maris |
author_role |
author |
author2 |
Masone, Diego Fernando Muñoz, Estela Maris |
author2_role |
author author |
dc.subject.none.fl_str_mv |
GABA GABA RECEPTORS AGEING CHOLESTEROL |
topic |
GABA GABA RECEPTORS AGEING CHOLESTEROL |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
GABA B receptors (GABABRs) are obligatory heterodimers which belong to the superfamily of G protein-coupled receptors (GPCRs). Age-related changes in membrane cholesterol levels modulate membrane fluidity, which in-turn influences GPCRs´ localization and function. We studied the GABABR and also a transmembrane transporter structurally homologous to KCC2. To characterize transient conformational changes over time, molecular dynamics simulations were performed using a neuronal plasma membrane (PM) model. Two different membrane cholesterol levels were evaluated: 45% and 10%, which intend to resemble the composition of adult and aged neuronal PMs, respectively. For experimental verification in both young and aged cerebella, we determined protein expression and distribution, and we assessed whether the two proteins interact with each other in vivo. Techniques were: western blots (WB), co-immunoprecipitation assays, and multiple immunolabeling followed by confocal microscopy. Our results suggest that the expression and spatial distribution of both proteins change as the cerebellum grows older. Based on our in silico analyses, we infer that a G protein-independent interaction does occur. Also, we confirmed that the two proteins are part of the same complex in the cerebellum. As our simulations indicate, we propose that the underlying mechanism implies transient conformational changes, which are highly dependent on cholesterol levels and are therefore affected by the aging process. Fil: Vásquez, Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina Fil: Masone, Diego Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina Fil: Muñoz, Estela Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina XXXIV Annual Meeting of Argentine Society for Research in Neurosciences Villa Carlos Paz Argentina Argentine Society for Research in Neurosciences |
description |
GABA B receptors (GABABRs) are obligatory heterodimers which belong to the superfamily of G protein-coupled receptors (GPCRs). Age-related changes in membrane cholesterol levels modulate membrane fluidity, which in-turn influences GPCRs´ localization and function. We studied the GABABR and also a transmembrane transporter structurally homologous to KCC2. To characterize transient conformational changes over time, molecular dynamics simulations were performed using a neuronal plasma membrane (PM) model. Two different membrane cholesterol levels were evaluated: 45% and 10%, which intend to resemble the composition of adult and aged neuronal PMs, respectively. For experimental verification in both young and aged cerebella, we determined protein expression and distribution, and we assessed whether the two proteins interact with each other in vivo. Techniques were: western blots (WB), co-immunoprecipitation assays, and multiple immunolabeling followed by confocal microscopy. Our results suggest that the expression and spatial distribution of both proteins change as the cerebellum grows older. Based on our in silico analyses, we infer that a G protein-independent interaction does occur. Also, we confirmed that the two proteins are part of the same complex in the cerebellum. As our simulations indicate, we propose that the underlying mechanism implies transient conformational changes, which are highly dependent on cholesterol levels and are therefore affected by the aging process. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/conferenceObject Reunión Journal http://purl.org/coar/resource_type/c_5794 info:ar-repo/semantics/documentoDeConferencia |
status_str |
publishedVersion |
format |
conferenceObject |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/202358 Dynamics of GABABR signaling: influence of cholesterol and aging; XXXIV Annual Meeting of Argentine Society for Research in Neurosciences ; Villa Carlos Paz; Argentina; 2019; 23-23 1759-0914 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/202358 |
identifier_str_mv |
Dynamics of GABABR signaling: influence of cholesterol and aging; XXXIV Annual Meeting of Argentine Society for Research in Neurosciences ; Villa Carlos Paz; Argentina; 2019; 23-23 1759-0914 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://journals.sagepub.com/doi/10.1177/1759091420979851 info:eu-repo/semantics/altIdentifier/doi/10.1177/1759091420979851 |
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info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc/2.5/ar/ |
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openAccess |
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application/pdf application/pdf application/pdf application/pdf |
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Internacional |
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SAGE Publications |
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SAGE Publications |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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