Varela, Lorena, Hendry, Alex C., cassar, Joseph, Martín-Escolano, Rubén, Cantoni, Diego, Ossa, Felipe, edwards, John C, abdul-salam, Vahitha, Ortega-Roldan, Jose L. (2022) A Zn2+-triggered two-step mechanism of CLIC1 membrane insertion and activation into chloride channels. Journal of Cell Science, 135 (15). Article Number jcs259704. ISSN 0021-9533. (doi:10.1242/jcs.259704) (KAR id:96744)
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Official URL: https://doi.org/10.1242/jcs.259704 |
Abstract
The chloride intracellular channel (CLIC) protein family displays the unique feature of altering its structure from a soluble form to a membrane-bound chloride channel. CLIC1, a member of this family, is found in the cytoplasm or in internal and plasma membranes, with membrane relocalisation linked to endothelial disfunction, tumour proliferation and metastasis. The molecular switch promoting CLIC1 activation remains under investigation. Here, cellular Cl− efflux assays and immunofluorescence microscopy studies have identified intracellular Zn2+ release as the trigger for CLIC1 activation and membrane insertion. Biophysical assays confirmed specific binding to Zn2+, inducing membrane association and enhancing Cl− efflux in a pH-dependent manner. Together, our results identify a two- step mechanism with Zn2+ binding as the molecular switch promoting CLIC1 membrane insertion, followed by pH-mediated activation of Cl− efflux.
Item Type: | Article |
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DOI/Identification number: | 10.1242/jcs.259704 |
Uncontrolled keywords: | Membrane protein, Chloride channel, Channel activation, Lipid–protein interaction, Biophysics |
Subjects: | Q Science |
Divisions: | Divisions > Division of Natural Sciences > Biosciences |
Funders: |
Fundación Alfonso Martín Escudero (https://ror.org/02897ye82)
Barts Charity (https://ror.org/0513pp416) Wellcome Trust (https://ror.org/029chgv08) |
Depositing User: | Jose Ortega Roldan |
Date Deposited: | 05 Sep 2022 13:52 UTC |
Last Modified: | 05 Nov 2024 13:01 UTC |
Resource URI: | https://kar.kent.ac.uk/id/eprint/96744 (The current URI for this page, for reference purposes) |
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