Please use this identifier to cite or link to this item:
https://hdl.handle.net/2445/174420
Title: | Functional consequences of the variable stoichiometry of the Kv1.3-KCNE4 complex |
Author: | Solé i Codina, Laura Sastre Martinez, Daniel Colomer-Molera, Magalí Vallejo Gracia, Albert Roig Merino, Sara Raquel Perez-Verdaguer, Mireia Lillo, Pilar Tamkun, Michael M. Felipe Campo, Antonio |
Keywords: | Canals de potassi Proteïnes Molècules Sistema immunitari Potassium channels Proteins Molecules Immune system |
Issue Date: | 2-May-2020 |
Publisher: | MDPI |
Abstract: | The voltage-gated potassium channel Kv1.3 plays a crucial role during the immune response. The channel forms oligomeric complexes by associating with several modulatory subunits. KCNE4, one of the five members of the KCNE family, binds to Kv1.3, altering channel activity and membrane expression. The association of KCNEs with Kv channels is the subject of numerous studies, and the stoichiometry of such associations has led to an ongoing debate. The number of KCNE4 subunits that can interact and modulate Kv1.3 is unknown. KCNE4 transfers important elements to the Kv1.3 channelosome that negatively regulate channel function, thereby fine-tuning leukocyte physiology. The aim of this study was to determine the stoichiometry of the functional Kv1.3-KCNE4 complex. We demonstrate that as many as four KCNE4 subunits can bind to the same Kv1.3 channel, indicating a variable Kv1.3-KCNE4 stoichiometry. While increasing the number of KCNE4 subunits steadily slowed the activation of the channel and decreased the abundance of Kv1.3 at the cell surface, the presence of a single KCNE4 peptide was suffcient for the cooperative enhancement of the inactivating function of the channel. This variable architecture, which depends on KCNE4 availability, differentially affects Kv1.3 function. Therefore, our data indicate that the physiological remodeling of KCNE4 triggers functional consequences for Kv1.3, thus affecting cell physiology. |
Note: | Reproducció del document publicat a: https://doi.org/10.3390/cells9051128 |
It is part of: | Cells, 2020, vol. 9(5), num. 1128 |
URI: | https://hdl.handle.net/2445/174420 |
Related resource: | https://doi.org/10.3390/cells9051128 |
ISSN: | 2073-4409 |
Appears in Collections: | Articles publicats en revistes (Institut de Biomedicina (IBUB)) Articles publicats en revistes (Bioquímica i Biomedicina Molecular) |
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