WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation.
Amphipathic Helix
Autophagosome
Autophagy
Kinase
WIPIs
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
16 Aug 2024
16 Aug 2024
Historique:
received:
15
12
2023
accepted:
04
07
2024
revised:
21
06
2024
medline:
17
8
2024
pubmed:
17
8
2024
entrez:
16
8
2024
Statut:
aheadofprint
Résumé
One of the key events in autophagy is the formation of a double-membrane phagophore, and many regulatory mechanisms underpinning this remain under investigation. WIPI2b is among the first proteins to be recruited to the phagophore and is essential for stimulating autophagy flux by recruiting the ATG12-ATG5-ATG16L1 complex, driving LC3 and GABARAP lipidation. Here, we set out to investigate how WIPI2b function is regulated by phosphorylation. We studied two phosphorylation sites on WIPI2b, S68 and S284. Phosphorylation at these sites plays distinct roles, regulating WIPI2b's association with ATG16L1 and the phagophore, respectively. We confirm WIPI2b is a novel ULK1 substrate, validated by the detection of endogenous phosphorylation at S284. Notably, S284 is situated within an 18-amino acid stretch, which, when in contact with liposomes, forms an amphipathic helix. Phosphorylation at S284 disrupts the formation of the amphipathic helix, hindering the association of WIPI2b with membranes and autophagosome formation. Understanding these intricacies in the regulatory mechanisms governing WIPI2b's association with its interacting partners and membranes, holds the potential to shed light on these complex processes, integral to phagophore biogenesis.
Identifiants
pubmed: 39152217
doi: 10.1038/s44319-024-00215-5
pii: 10.1038/s44319-024-00215-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust
ID : CC2134
Pays : United Kingdom
Organisme : Cancer Research UK (CRUK)
ID : CC1068
Organisme : Wellcome Trust
ID : CC2134
Pays : United Kingdom
Organisme : UKRI | Medical Research Council (MRC)
ID : CC1068
Organisme : Wellcome Trust
ID : CC2134
Pays : United Kingdom
Organisme : Wellcome Trust (WT)
ID : CC1068
Informations de copyright
© 2024. The Author(s).
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