Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros










Base de datos
Intervalo de año de publicación
1.
Biochem Pharmacol ; 185: 114427, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33513340

RESUMEN

Optineurin (OPTN) is a multifunctional protein that mediates a network of cellular processes regulating membrane trafficking, inflammatory responses and autophagy. The OPTN-rich interactome includes Group I metabotropic glutamate receptors (mGluR1 and 5), members of the Gαq/11 protein receptor family. Recent evidence has shown that mGluR5, in addition to its canonical Gαq/11 protein-coupled signaling, regulates autophagic machinery via mTOR/ULK1 and GSK3ß/ZBTB16 pathways in both Alzheimer's and Huntington's disease mouse models. Despite its potential involvement, the role of OPTN in mediating mGluR5 downstream signaling cascades remains largely unknown. Here, we employed a CRISPR/Cas9 OPTN-deficient STHdhQ7/Q7 striatal cell line and global OPTN knockout mice to investigate whether Optn gene deletion alters both mGluR5 canonical and noncanonical signaling. We find that OPTN is required for mGluR5-activated Ca2+ flux and ERK1/2 signaling following receptor activation in STHdhQ7/Q7 cells and acute hippocampal slices. Deletion of OPTN impairs both GSK3ß/ZBTB16 and mTOR/ULK1 autophagic signaling in STHdhQ7/Q7 cells. Furthermore, mGluR5-dependent regulation of GSK3ß/ZBTB16 and mTOR/ULK1 autophagic signaling is impaired in hippocampal slices of OPTN knockout mice. Overall, we show that the crosstalk between OPTN and mGluR5 can have major implication on receptor signaling and therefore potentially contribute to the pathophysiology of neurodegenerative diseases.


Asunto(s)
Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Proteínas de Ciclo Celular/deficiencia , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Proteínas de Transporte de Membrana/deficiencia , Proteína de la Leucemia Promielocítica con Dedos de Zinc/metabolismo , Receptor del Glutamato Metabotropico 5/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Animales , Autofagia/fisiología , Hipocampo/metabolismo , Hipocampo/patología , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...