KCNE4-dependent functional consequences of Kv1.3-related leukocyte physiology

Abstract 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...

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Autores principales:	Albert Vallejo-Gracia, Daniel Sastre, Magalí Colomer-Molera, Laura Solé, María Navarro-Pérez, Jesusa Capera, Sara R. Roig, Oriol Pedrós-Gámez, Irene Estadella, Orsolya Szilágyi, Gyorgy Panyi, Péter Hajdú, Antonio Felipe
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e253620662d849e695553c79f61cab76
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spelling	oai:doaj.org-article:e253620662d849e695553c79f61cab762021-12-02T15:33:00ZKCNE4-dependent functional consequences of Kv1.3-related leukocyte physiology10.1038/s41598-021-94015-92045-2322https://doaj.org/article/e253620662d849e695553c79f61cab762021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94015-9https://doaj.org/toc/2045-2322Abstract 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.Albert Vallejo-GraciaDaniel SastreMagalí Colomer-MoleraLaura SoléMaría Navarro-PérezJesusa CaperaSara R. RoigOriol Pedrós-GámezIrene EstadellaOrsolya SzilágyiGyorgy PanyiPéter HajdúAntonio FelipeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Albert Vallejo-Gracia Daniel Sastre Magalí Colomer-Molera Laura Solé María Navarro-Pérez Jesusa Capera Sara R. Roig Oriol Pedrós-Gámez Irene Estadella Orsolya Szilágyi Gyorgy Panyi Péter Hajdú Antonio Felipe KCNE4-dependent functional consequences of Kv1.3-related leukocyte physiology
description	Abstract 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.
format	article
author	Albert Vallejo-Gracia Daniel Sastre Magalí Colomer-Molera Laura Solé María Navarro-Pérez Jesusa Capera Sara R. Roig Oriol Pedrós-Gámez Irene Estadella Orsolya Szilágyi Gyorgy Panyi Péter Hajdú Antonio Felipe
author_facet	Albert Vallejo-Gracia Daniel Sastre Magalí Colomer-Molera Laura Solé María Navarro-Pérez Jesusa Capera Sara R. Roig Oriol Pedrós-Gámez Irene Estadella Orsolya Szilágyi Gyorgy Panyi Péter Hajdú Antonio Felipe
author_sort	Albert Vallejo-Gracia
title	KCNE4-dependent functional consequences of Kv1.3-related leukocyte physiology
title_short	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_sort	kcne4-dependent functional consequences of kv1.3-related leukocyte physiology
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e253620662d849e695553c79f61cab76
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KCNE4-dependent functional consequences of Kv1.3-related leukocyte physiology

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