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

• Main Authors: 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
• Format: Article
• Language: English
• Published: Nature Publishing Group 2021-07-01
• Series: Scientific Reports
• Online Access: https://doi.org/10.1038/s41598-021-94015-9

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.