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The Role of the Carboxyl Terminus Helix C-D Linker in Regulating KCNQ3 K(+) Current Amplitudes by Controlling Channel Trafficking
In the central and peripheral nervous system, the assembly of KCNQ3 with KCNQ2 as mostly heteromers, but also homomers, underlies “M-type” currents, a slowly-activating voltage-gated K(+) current that plays a dominant role in neuronal excitability. KCNQ3 homomers yield much smaller currents compared...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687061/ https://www.ncbi.nlm.nih.gov/pubmed/26692086 http://dx.doi.org/10.1371/journal.pone.0145367 |
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author | Choveau, Frank S. Zhang, Jie Bierbower, Sonya M. Sharma, Ramaswamy Shapiro, Mark S. |
author_facet | Choveau, Frank S. Zhang, Jie Bierbower, Sonya M. Sharma, Ramaswamy Shapiro, Mark S. |
author_sort | Choveau, Frank S. |
collection | PubMed |
description | In the central and peripheral nervous system, the assembly of KCNQ3 with KCNQ2 as mostly heteromers, but also homomers, underlies “M-type” currents, a slowly-activating voltage-gated K(+) current that plays a dominant role in neuronal excitability. KCNQ3 homomers yield much smaller currents compared to KCNQ2 or KCNQ4 homomers and KCNQ2/3 heteromers. This smaller current has been suggested to result either from divergent channel surface expression or from a pore that is more unstable in KCNQ3. Channel surface expression has been shown to be governed by the distal part of the C-terminus in which helices C and D are critical for channel trafficking and assembly. A sequence alignment of this region in KCNQ channels shows that KCNQ3 possesses a longer linker between helix C and D compared to the other KCNQ subunits. Here, we investigate the role of the extra residues of this linker on KCNQ channel expression. Deletion of these residues increased KCNQ3 current amplitudes. Total internal reflection fluorescence imaging and plasma membrane protein assays suggest that the increase in current is due to a higher surface expression of the channels. Conversely, introduction of the extra residues into the linker between helices C and D of KCNQ4 reduced current amplitudes by decreasing the number of KCNQ4 channels at the plasma membrane. Confocal imaging suggests a higher fraction of channels, which possess the extra residues of helix C-D linker, were retained within the endoplasmic reticulum. Such retention does not appear to lead to protein accumulation and activation of the unfolded protein response that regulates protein folding and maintains endoplasmic reticulum homeostasis. Taken together, we conclude that extra helix C-D linker residues play a role in KCNQ3 current amplitudes by controlling the exit of the channel from the endoplasmic reticulum. |
format | Online Article Text |
id | pubmed-4687061 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-46870612016-01-07 The Role of the Carboxyl Terminus Helix C-D Linker in Regulating KCNQ3 K(+) Current Amplitudes by Controlling Channel Trafficking Choveau, Frank S. Zhang, Jie Bierbower, Sonya M. Sharma, Ramaswamy Shapiro, Mark S. PLoS One Research Article In the central and peripheral nervous system, the assembly of KCNQ3 with KCNQ2 as mostly heteromers, but also homomers, underlies “M-type” currents, a slowly-activating voltage-gated K(+) current that plays a dominant role in neuronal excitability. KCNQ3 homomers yield much smaller currents compared to KCNQ2 or KCNQ4 homomers and KCNQ2/3 heteromers. This smaller current has been suggested to result either from divergent channel surface expression or from a pore that is more unstable in KCNQ3. Channel surface expression has been shown to be governed by the distal part of the C-terminus in which helices C and D are critical for channel trafficking and assembly. A sequence alignment of this region in KCNQ channels shows that KCNQ3 possesses a longer linker between helix C and D compared to the other KCNQ subunits. Here, we investigate the role of the extra residues of this linker on KCNQ channel expression. Deletion of these residues increased KCNQ3 current amplitudes. Total internal reflection fluorescence imaging and plasma membrane protein assays suggest that the increase in current is due to a higher surface expression of the channels. Conversely, introduction of the extra residues into the linker between helices C and D of KCNQ4 reduced current amplitudes by decreasing the number of KCNQ4 channels at the plasma membrane. Confocal imaging suggests a higher fraction of channels, which possess the extra residues of helix C-D linker, were retained within the endoplasmic reticulum. Such retention does not appear to lead to protein accumulation and activation of the unfolded protein response that regulates protein folding and maintains endoplasmic reticulum homeostasis. Taken together, we conclude that extra helix C-D linker residues play a role in KCNQ3 current amplitudes by controlling the exit of the channel from the endoplasmic reticulum. Public Library of Science 2015-12-21 /pmc/articles/PMC4687061/ /pubmed/26692086 http://dx.doi.org/10.1371/journal.pone.0145367 Text en © 2015 Choveau et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Choveau, Frank S. Zhang, Jie Bierbower, Sonya M. Sharma, Ramaswamy Shapiro, Mark S. The Role of the Carboxyl Terminus Helix C-D Linker in Regulating KCNQ3 K(+) Current Amplitudes by Controlling Channel Trafficking |
title | The Role of the Carboxyl Terminus Helix C-D Linker in Regulating KCNQ3 K(+) Current Amplitudes by Controlling Channel Trafficking |
title_full | The Role of the Carboxyl Terminus Helix C-D Linker in Regulating KCNQ3 K(+) Current Amplitudes by Controlling Channel Trafficking |
title_fullStr | The Role of the Carboxyl Terminus Helix C-D Linker in Regulating KCNQ3 K(+) Current Amplitudes by Controlling Channel Trafficking |
title_full_unstemmed | The Role of the Carboxyl Terminus Helix C-D Linker in Regulating KCNQ3 K(+) Current Amplitudes by Controlling Channel Trafficking |
title_short | The Role of the Carboxyl Terminus Helix C-D Linker in Regulating KCNQ3 K(+) Current Amplitudes by Controlling Channel Trafficking |
title_sort | role of the carboxyl terminus helix c-d linker in regulating kcnq3 k(+) current amplitudes by controlling channel trafficking |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687061/ https://www.ncbi.nlm.nih.gov/pubmed/26692086 http://dx.doi.org/10.1371/journal.pone.0145367 |
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