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GlialCAM, a CLC-2 Cl(-) Channel Subunit, Activates the Slow Gate of CLC Chloride Channels
GlialCAM, a glial cell adhesion molecule mutated in megalencephalic leukoencephalopathy with subcortical cysts, targets the CLC-2 Cl(-) channel to cell contacts in glia and activates CLC-2 currents in vitro and in vivo. We found that GlialCAM clusters all CLC channels at cell contacts in vitro and t...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Biophysical Society
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156679/ https://www.ncbi.nlm.nih.gov/pubmed/25185546 http://dx.doi.org/10.1016/j.bpj.2014.07.040 |
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author | Jeworutzki, Elena Lagostena, Laura Elorza-Vidal, Xabier López-Hernández, Tania Estévez, Raúl Pusch, Michael |
author_facet | Jeworutzki, Elena Lagostena, Laura Elorza-Vidal, Xabier López-Hernández, Tania Estévez, Raúl Pusch, Michael |
author_sort | Jeworutzki, Elena |
collection | PubMed |
description | GlialCAM, a glial cell adhesion molecule mutated in megalencephalic leukoencephalopathy with subcortical cysts, targets the CLC-2 Cl(-) channel to cell contacts in glia and activates CLC-2 currents in vitro and in vivo. We found that GlialCAM clusters all CLC channels at cell contacts in vitro and thus studied GlialCAM interaction with CLC channels to investigate the mechanism of functional activation. GlialCAM slowed deactivation kinetics of CLC-Ka/barttin channels and increased CLC-0 currents opening the common gate and slowing its deactivation. No functional effect was seen for common gate deficient CLC-0 mutants. Similarly, GlialCAM targets the common gate deficient CLC-2 mutant E211V/H816A to cell contacts, without altering its function. Thus, GlialCAM is able to interact with all CLC channels tested, targeting them to cell junctions and activating them by stabilizing the open configuration of the common gate. These results are important to better understand the physiological role of GlialCAM/CLC-2 interaction. |
format | Online Article Text |
id | pubmed-4156679 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Biophysical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-41566792015-01-08 GlialCAM, a CLC-2 Cl(-) Channel Subunit, Activates the Slow Gate of CLC Chloride Channels Jeworutzki, Elena Lagostena, Laura Elorza-Vidal, Xabier López-Hernández, Tania Estévez, Raúl Pusch, Michael Biophys J Channels and Transporters GlialCAM, a glial cell adhesion molecule mutated in megalencephalic leukoencephalopathy with subcortical cysts, targets the CLC-2 Cl(-) channel to cell contacts in glia and activates CLC-2 currents in vitro and in vivo. We found that GlialCAM clusters all CLC channels at cell contacts in vitro and thus studied GlialCAM interaction with CLC channels to investigate the mechanism of functional activation. GlialCAM slowed deactivation kinetics of CLC-Ka/barttin channels and increased CLC-0 currents opening the common gate and slowing its deactivation. No functional effect was seen for common gate deficient CLC-0 mutants. Similarly, GlialCAM targets the common gate deficient CLC-2 mutant E211V/H816A to cell contacts, without altering its function. Thus, GlialCAM is able to interact with all CLC channels tested, targeting them to cell junctions and activating them by stabilizing the open configuration of the common gate. These results are important to better understand the physiological role of GlialCAM/CLC-2 interaction. The Biophysical Society 2014-09-02 2014-09-02 /pmc/articles/PMC4156679/ /pubmed/25185546 http://dx.doi.org/10.1016/j.bpj.2014.07.040 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). |
spellingShingle | Channels and Transporters Jeworutzki, Elena Lagostena, Laura Elorza-Vidal, Xabier López-Hernández, Tania Estévez, Raúl Pusch, Michael GlialCAM, a CLC-2 Cl(-) Channel Subunit, Activates the Slow Gate of CLC Chloride Channels |
title | GlialCAM, a CLC-2 Cl(-) Channel Subunit, Activates the Slow Gate of CLC Chloride Channels |
title_full | GlialCAM, a CLC-2 Cl(-) Channel Subunit, Activates the Slow Gate of CLC Chloride Channels |
title_fullStr | GlialCAM, a CLC-2 Cl(-) Channel Subunit, Activates the Slow Gate of CLC Chloride Channels |
title_full_unstemmed | GlialCAM, a CLC-2 Cl(-) Channel Subunit, Activates the Slow Gate of CLC Chloride Channels |
title_short | GlialCAM, a CLC-2 Cl(-) Channel Subunit, Activates the Slow Gate of CLC Chloride Channels |
title_sort | glialcam, a clc-2 cl(-) channel subunit, activates the slow gate of clc chloride channels |
topic | Channels and Transporters |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156679/ https://www.ncbi.nlm.nih.gov/pubmed/25185546 http://dx.doi.org/10.1016/j.bpj.2014.07.040 |
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