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KCNE4-dependent functional consequences of Kv1.3-related leukocyte physiology. Vallejo-Gracia, Albert Sastre Martinez, Daniel Colomer-Molera, Magalí Solé, Laura Navarro-Pérez, María Capera Aragonés, Jesusa Roig, Sara R. Pedrós-Gámez, Oriol Estadella, Irene Szilágyi, Orsolya Panyi, Gyorgy Hajdú, Péter Felipe Campo, Antonio Canals de potassi Sistema immunitari Leucòcits Cèl·lules T Potassium channels Immune system Leucocytes T cells 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 fne-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 afected 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 fne-tunes immune system physiology by modulating Kv1.3-associated leukocyte functions. 2022-06-01T16:43:21Z 2022-06-01T16:43:21Z 2021-07-16 2022-06-01T16:43:22Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 2045-2322 https://hdl.handle.net/2445/186239 715777 eng Reproducció del document publicat a: https://doi.org/10.1038/s41598-021-94015-9 Scientific Reports, 2021, vol. 11, p. 14632 https://doi.org/10.1038/s41598-021-94015-9 cc-by (c) Vallejo-Gracia, Albert et al., 2021 https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess 14 p. application/pdf Nature Publishing Group Articles publicats en revistes (Bioquímica i Biomedicina Molecular)