KCNE4-dependent functional consequences of Kv1.3-related leukocyte physiology
The voltage-dependent potassium channel Kv1.3 plays essential roles in the immune system, participating in leukocyte activation, proliferation and apoptosis. The regulatory subunit KCNE4 acts as an ancillary peptide of Kv1.3, modulates K+ currents and controls channel abundance at the cell surface....
Main Authors: | , , , , , , , , , , , , |
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Format: | Journal article |
Language: | English |
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Springer Nature
2021
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_version_ | 1797069512769536000 |
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author | Vallejo-Gracia, A Sastre, D Colomer-Molera, M Solé, L Navarro-Pérez, M Capera Aragones, JCA Roig, SR Pedrós-Gámez, O Estadella, I Szilágyi, O Panyi, G Hajdú, P Felipe, A |
author_facet | Vallejo-Gracia, A Sastre, D Colomer-Molera, M Solé, L Navarro-Pérez, M Capera Aragones, JCA Roig, SR Pedrós-Gámez, O Estadella, I Szilágyi, O Panyi, G Hajdú, P Felipe, A |
author_sort | Vallejo-Gracia, A |
collection | OXFORD |
description | The voltage-dependent potassium channel Kv1.3 plays essential roles in the immune system, participating in leukocyte activation, proliferation and apoptosis. The regulatory subunit KCNE4 acts as an ancillary peptide of Kv1.3, modulates K+ currents and controls channel abundance at the cell surface. KCNE4-dependent regulation of the oligomeric complex fine-tunes the physiological role of Kv1.3. Thus, KCNE4 is crucial for Ca2+-dependent Kv1.3-related leukocyte functions. To better understand the role of KCNE4 in the regulation of the immune system, we manipulated its expression in various leukocyte cell lines. Jurkat T lymphocytes exhibit low KCNE4 levels, whereas CY15 dendritic cells, a model of professional antigen-presenting cells, robustly express KCNE4. When the cellular KCNE4 abundance was increased in T cells, the interaction between KCNE4 and Kv1.3 affected important T cell physiological features, such as channel rearrangement in the immunological synapse, cell growth, apoptosis and activation, as indicated by decreased IL-2 production. Conversely, ablation of KCNE4 in dendritic cells augmented proliferation. Furthermore, the LPS-dependent activation of CY15 cells, which induced Kv1.3 but not KCNE4, increased the Kv1.3-KCNE4 ratio and increased the expression of free Kv1.3 without KCNE4 interaction. Our results demonstrate that KCNE4 is a pivotal regulator of the Kv1.3 channelosome, which fine-tunes immune system physiology by modulating Kv1.3-associated leukocyte functions. |
first_indexed | 2024-03-06T22:25:34Z |
format | Journal article |
id | oxford-uuid:56906648-ef8d-4825-9954-52547256183f |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-06T22:25:34Z |
publishDate | 2021 |
publisher | Springer Nature |
record_format | dspace |
spelling | oxford-uuid:56906648-ef8d-4825-9954-52547256183f2022-03-26T16:51:00ZKCNE4-dependent functional consequences of Kv1.3-related leukocyte physiologyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:56906648-ef8d-4825-9954-52547256183fEnglishSymplectic ElementsSpringer Nature2021Vallejo-Gracia, ASastre, DColomer-Molera, MSolé, LNavarro-Pérez, MCapera Aragones, JCARoig, SRPedrós-Gámez, OEstadella, ISzilágyi, OPanyi, GHajdú, PFelipe, AThe voltage-dependent potassium channel Kv1.3 plays essential roles in the immune system, participating in leukocyte activation, proliferation and apoptosis. The regulatory subunit KCNE4 acts as an ancillary peptide of Kv1.3, modulates K+ currents and controls channel abundance at the cell surface. KCNE4-dependent regulation of the oligomeric complex fine-tunes the physiological role of Kv1.3. Thus, KCNE4 is crucial for Ca2+-dependent Kv1.3-related leukocyte functions. To better understand the role of KCNE4 in the regulation of the immune system, we manipulated its expression in various leukocyte cell lines. Jurkat T lymphocytes exhibit low KCNE4 levels, whereas CY15 dendritic cells, a model of professional antigen-presenting cells, robustly express KCNE4. When the cellular KCNE4 abundance was increased in T cells, the interaction between KCNE4 and Kv1.3 affected important T cell physiological features, such as channel rearrangement in the immunological synapse, cell growth, apoptosis and activation, as indicated by decreased IL-2 production. Conversely, ablation of KCNE4 in dendritic cells augmented proliferation. Furthermore, the LPS-dependent activation of CY15 cells, which induced Kv1.3 but not KCNE4, increased the Kv1.3-KCNE4 ratio and increased the expression of free Kv1.3 without KCNE4 interaction. Our results demonstrate that KCNE4 is a pivotal regulator of the Kv1.3 channelosome, which fine-tunes immune system physiology by modulating Kv1.3-associated leukocyte functions. |
spellingShingle | Vallejo-Gracia, A Sastre, D Colomer-Molera, M Solé, L Navarro-Pérez, M Capera Aragones, JCA Roig, SR Pedrós-Gámez, O Estadella, I Szilágyi, O Panyi, G Hajdú, P Felipe, A KCNE4-dependent functional consequences of Kv1.3-related leukocyte physiology |
title | KCNE4-dependent functional consequences of Kv1.3-related leukocyte physiology |
title_full | KCNE4-dependent functional consequences of Kv1.3-related leukocyte physiology |
title_fullStr | KCNE4-dependent functional consequences of Kv1.3-related leukocyte physiology |
title_full_unstemmed | KCNE4-dependent functional consequences of Kv1.3-related leukocyte physiology |
title_short | KCNE4-dependent functional consequences of Kv1.3-related leukocyte physiology |
title_sort | kcne4 dependent functional consequences of kv1 3 related leukocyte physiology |
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