Chloride intracellular channel (CLIC) proteins function as fusogens.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 Mar 2024
07 Mar 2024
Historique:
received:
27
08
2023
accepted:
19
02
2024
medline:
8
3
2024
pubmed:
8
3
2024
entrez:
7
3
2024
Statut:
epublish
Résumé
Chloride Intracellular Channel (CLIC) family members uniquely transition between soluble and membrane-associated conformations. Despite decades of extensive functional and structural studies, CLICs' function as ion channels remains debated, rendering our understanding of their physiological role incomplete. Here, we expose the function of CLIC5 as a fusogen. We demonstrate that purified CLIC5 directly interacts with the membrane and induces fusion, as reflected by increased liposomal diameter and lipid and content mixing between liposomes. Moreover, we show that this activity is facilitated by acidic pH, a known trigger for CLICs' transition to a membrane-associated conformation, and that increased exposure of the hydrophobic inter-domain interface is crucial for this process. Finally, mutation of a conserved hydrophobic interfacial residue diminishes the fusogenic activity of CLIC5 in vitro and impairs excretory canal extension in C. elegans in vivo. Together, our results unravel the long-sought physiological role of these enigmatic proteins.
Identifiants
pubmed: 38453905
doi: 10.1038/s41467-024-46301-z
pii: 10.1038/s41467-024-46301-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2085Subventions
Organisme : Israel Science Foundation (ISF)
ID : 1721/16
Organisme : Israel Science Foundation (ISF)
ID : 1653/21
Organisme : Israel Science Foundation (ISF)
ID : 3308/20
Organisme : Israel Cancer Research Fund (Israel Cancer Research Fund, Inc.)
ID : 01214
Organisme : Israel Cancer Research Fund (Israel Cancer Research Fund, Inc.)
ID : 19202
Organisme : Israel Cancer Association (ICA)
ID : 20230029
Organisme : Ministerstvo školstva, vedy, výskumu a športu Slovenskej republiky (Ministry of Education, Science, Research and Sport of the Slovak Republic)
ID : CZ.1.05/1.1.00/02.0109
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 731077
Informations de copyright
© 2024. The Author(s).
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