Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Jeworutzki, Elena, Lagostena, Laura, Elorza-Vidal, Xabier, López-Hernández, Tania, Estévez, Raúl, Pusch, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Biophysical Society 2014
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
_version_ 1782333774241988608
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
work_keys_str_mv AT jeworutzkielena glialcamaclc2clchannelsubunitactivatestheslowgateofclcchloridechannels
AT lagostenalaura glialcamaclc2clchannelsubunitactivatestheslowgateofclcchloridechannels
AT elorzavidalxabier glialcamaclc2clchannelsubunitactivatestheslowgateofclcchloridechannels
AT lopezhernandeztania glialcamaclc2clchannelsubunitactivatestheslowgateofclcchloridechannels
AT estevezraul glialcamaclc2clchannelsubunitactivatestheslowgateofclcchloridechannels
AT puschmichael glialcamaclc2clchannelsubunitactivatestheslowgateofclcchloridechannels