Early proteostasis of caveolins synchronizes trafficking, degradation, and oligomerization to prevent toxic aggregation.
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
04 09 2023
04 09 2023
Historique:
received:
07
04
2022
revised:
05
04
2023
accepted:
09
06
2023
medline:
2
8
2023
pubmed:
1
8
2023
entrez:
1
8
2023
Statut:
ppublish
Résumé
Caveolin-1 (CAV1) and CAV3 are membrane-sculpting proteins driving the formation of the plasma membrane (PM) caveolae. Within the PM mosaic environment, caveola assembly is unique as it requires progressive oligomerization of newly synthesized caveolins while trafficking through the biosynthetic-secretory pathway. Here, we have investigated these early events by combining structural, biochemical, and microscopy studies. We uncover striking trafficking differences between caveolins, with CAV1 rapidly exported to the Golgi and PM while CAV3 is initially retained in the endoplasmic reticulum and laterally moves into lipid droplets. The levels of caveolins in the endoplasmic reticulum are controlled by proteasomal degradation, and only monomeric/low oligomeric caveolins are exported into the cis-Golgi with higher-order oligomers assembling beyond this compartment. When any of those early proteostatic mechanisms are compromised, chemically or genetically, caveolins tend to accumulate along the secretory pathway forming non-functional aggregates, causing organelle damage and triggering cellular stress. Accordingly, we propose a model in which disrupted proteostasis of newly synthesized caveolins contributes to pathogenesis.
Identifiants
pubmed: 37526691
pii: 276141
doi: 10.1083/jcb.202204020
pmc: PMC10394380
pii:
doi:
Substances chimiques
Caveolins
0
Caveolin 1
0
Membrane Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023 Morales-Paytuví et al.
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