Unconventional secretion factor GRASP55 is increased by pharmacological unfolded protein response inducers in neurons.
Astrocytes
/ drug effects
Endoplasmic Reticulum Stress
Endoribonucleases
/ genetics
Gene Expression
Golgi Matrix Proteins
/ genetics
Humans
Neurons
/ drug effects
Protein Serine-Threonine Kinases
/ genetics
Protein Transport
Unfolded Protein Response
/ drug effects
X-Box Binding Protein 1
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
07 02 2019
07 02 2019
Historique:
received:
06
07
2018
accepted:
19
12
2018
entrez:
9
2
2019
pubmed:
9
2
2019
medline:
20
8
2020
Statut:
epublish
Résumé
Accumulation of misfolded proteins in the endoplasmic reticulum (ER), defined as ER stress, results in activation of the unfolded protein response (UPR). UPR activation is commonly observed in neurodegenerative diseases. ER stress can trigger unconventional secretion mediated by Golgi reassembly and stacking proteins (GRASP) relocalization in cell lines. Here we study the regulation of GRASP55 by the UPR upon pharmacological induction of ER stress in primary mouse neurons. We demonstrate that UPR activation induces mRNA and protein expression of GRASP55, but not GRASP65, in cortical neurons. UPR activation does not result in relocalization of GRASP55. UPR-induced GRASP55 expression is reduced by inhibition of the PERK pathway of the UPR and abolished by inhibition of the endonuclease activity of the UPR transducer IRE1. Expression of the IRE1 target XBP1s in the absence of ER stress is not sufficient to increase GRASP55 expression. Knockdown of GRASP55 affects neither induction nor recovery of the UPR. We conclude that the UPR regulates the unconventional secretion factor GRASP55 via a mechanism that requires the IRE1 and the PERK pathway of the UPR in neurons.
Identifiants
pubmed: 30733486
doi: 10.1038/s41598-018-38146-6
pii: 10.1038/s41598-018-38146-6
pmc: PMC6367349
doi:
Substances chimiques
GORASP2 protein, human
0
Golgi Matrix Proteins
0
X-Box Binding Protein 1
0
ERN1 protein, human
EC 2.7.11.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
Endoribonucleases
EC 3.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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