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....

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Main Authors: 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
Format: Journal article
Language:English
Published: Springer Nature 2021
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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.
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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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