Evento
Dynamics of GABABR signaling: influence of cholesterol and aging
Tipo del evento:
Reunión
Nombre del evento:
XXXIV Annual Meeting of Argentine Society for Research in Neurosciences
Fecha del evento:
03/10/2019
Institución Organizadora:
Argentine Society for Research in Neurosciences;
Título de la revista:
ASN Neuro
Editorial:
SAGE Publications
ISSN:
1759-0914
Idioma:
Inglés
Clasificación temática:
Resumen
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.
Palabras clave:
GABA
,
GABA RECEPTORS
,
AGEING
,
CHOLESTEROL
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Identificadores
Colecciones
Eventos(IHEM)
Eventos de INST. HISTOLOGIA Y EMBRIOLOGIA DE MEND DR.M.BURGOS
Eventos de INST. HISTOLOGIA Y EMBRIOLOGIA DE MEND DR.M.BURGOS
Citación
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
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