Activation of endoplasmic reticulum stress in premature aging via the inner nuclear membrane protein SUN2.
CP: Cell biology
ER stress
Hutchinson-Gilford progeria syndrome
chaperones
transmembrane proteins
unfolded protein response
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
30 05 2023
30 05 2023
Historique:
received:
14
07
2022
revised:
08
03
2023
accepted:
03
05
2023
medline:
5
6
2023
pubmed:
21
5
2023
entrez:
21
5
2023
Statut:
ppublish
Résumé
One of the major cellular mechanisms to ensure cellular protein homeostasis is the endoplasmic reticulum (ER) stress response. This pathway is triggered by accumulation of misfolded proteins in the ER lumen. The ER stress response is also activated in the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). Here, we explore the mechanism of activation of the ER stress response in HGPS. We find that aggregation of the diseases-causing progerin protein at the nuclear envelope triggers ER stress. Induction of ER stress is dependent on the inner nuclear membrane protein SUN2 and its ability to cluster in the nuclear membrane. Our observations suggest that the presence of nucleoplasmic protein aggregates can be sensed, and signaled to the ER lumen, via clustering of SUN2. These results identify a mechanism of communication between the nucleus and the ER and provide insight into the molecular disease mechanisms of HGPS.
Identifiants
pubmed: 37210724
pii: S2211-1247(23)00545-4
doi: 10.1016/j.celrep.2023.112534
pmc: PMC10280311
mid: NIHMS1905399
pii:
doi:
Substances chimiques
Membrane Proteins
0
Lamin Type A
0
SUN2 protein, human
0
Intracellular Signaling Peptides and Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
112534Subventions
Organisme : Intramural NIH HHS
ID : Z01 BC010309
Pays : United States
Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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