Ubiquitylation of BBSome is required for ciliary assembly and signaling.
BBSome
cAMP
cilium
praja2
ubiquitin
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
05 04 2023
05 04 2023
Historique:
revised:
27
12
2022
received:
10
06
2022
accepted:
17
01
2023
medline:
6
4
2023
pubmed:
7
2
2023
entrez:
6
2
2023
Statut:
ppublish
Résumé
Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinal degeneration, obesity, renal abnormalities, postaxial polydactyly, and developmental defects. Genes mutated in BBS encode for components and regulators of the BBSome, an octameric complex that controls the trafficking of cargos and receptors within the primary cilium. Although both structure and function of the BBSome have been extensively studied, the impact of ubiquitin signaling on BBSome is largely unknown. We identify the E3 ubiquitin ligase PJA2 as a novel resident of the ciliary compartment and regulator of the BBSome. Upon GPCR-cAMP stimulation, PJA2 ubiquitylates BBSome subunits. We demonstrate that ubiquitylation of BBS1 at lysine 143 increases the stability of the BBSome and promotes its binding to BBS3, an Arf-like GTPase protein controlling the targeting of the BBSome to the ciliary membrane. Downregulation of PJA2 or expression of a ubiquitylation-defective BBS1 mutant (BBS1
Identifiants
pubmed: 36744302
doi: 10.15252/embr.202255571
pmc: PMC10074118
doi:
Substances chimiques
Receptors, G-Protein-Coupled
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e55571Subventions
Organisme : Associazione Italiana per la Ricerca sul Cancro (AIRC)
ID : IG2018-ID22062
Organisme : EC|European Regional Development Fund (ERDF)
Organisme : International Retinal Research Foundation (IRRF)
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR)
ID : D26C18000260005
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR)
ID : 2017CY3J3W
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR)
ID : 2017237P5x
Organisme : National Center for Gene Therapy and Drugs based on RNA Technology
ID : E63C22000940007
Organisme : University of Pennsylvania Orphan Disease Center in partnership with Choroideremia Research Foundation
ID : MDBR-21-103-CHM
Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
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