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Chloride intracellular channel (CLIC) proteins function as fusogens

B. Manori, A. Vaknin, P. Vaňková, A. Nitzan, R. Zaidel-Bar, P. Man, M. Giladi, Y. Haitin

. 2024 ; 15 (1) : 2085. [pub] 20240307

Language English Country England, Great Britain

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc24006774

Grant support
1721/16 Israel Science Foundation (ISF)
1653/21 Israel Science Foundation (ISF)
3308/20 Israel Science Foundation (ISF)
01214 Israel Cancer Research Fund (Israel Cancer Research Fund, Inc.)
19202 Israel Cancer Research Fund (Israel Cancer Research Fund, Inc.)
20230029 Israel Cancer Association (ICA)
CZ.1.05/1.1.00/02.0109 Ministerstvo školstva, vedy, výskumu a športu Slovenskej republiky (Ministry of Education, Science, Research and Sport of the Slovak Republic)
731077 EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)

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.

References provided by Crossref.org

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$a Vaknin, Alisa $u School of Chemistry, Raymond & Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, 6997801, Tel Aviv, Israel
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$a Nitzan, Anat $u Department of Cell and Developmental Biology, Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 6997801, Israel
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