Loss-of-Function Piezo1 Mutations Display Altered Stability Driven by Ubiquitination and Proteasomal Degradation.
mechanosensation
post-translational modification (PMT)
proteasomal degradation
protein biosynthesis
ubiquitiantion
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2021
2021
Historique:
received:
29
08
2021
accepted:
03
11
2021
entrez:
6
12
2021
pubmed:
7
12
2021
medline:
7
12
2021
Statut:
epublish
Résumé
Missense mutations in the gene that encodes for the mechanically-gated ion channel Piezo1 have been linked to a number of diseases. Gain-of-function variants are linked to a hereditary anaemia and loss-of-function variants have been linked to generalized lymphatic dysplasia and bicuspid aortic valve. Two previously characterized mutations, S217L and G2029R, both exhibit reduced plasma membrane trafficking. Here we show that both mutations also display reduced stability and higher turnover rates than wild-type Piezo1 channels. This occurs through increased ubiquitination and subsequent proteasomal degradation. Congruent with this, proteasome inhibition using
Identifiants
pubmed: 34867393
doi: 10.3389/fphar.2021.766416
pii: 766416
pmc: PMC8640252
doi:
Types de publication
Journal Article
Langues
eng
Pagination
766416Informations de copyright
Copyright © 2021 Zhou, Li, Martinac and Cox.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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