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Functional Consequences of the Variable Stoichiometry of the Kv1.3-KCNE4 Complex

Solé, Laura and Sastre, Daniel and Colomer-Molera, Magalí and Vallejo-Gracia, Albert and Roig, Sara R. and Pérez-Verdaguer, Mireia and Lillo, Pilar and Tamkun, Michael M. and Felipe, Antonio (2020) Functional Consequences of the Variable Stoichiometry of the Kv1.3-KCNE4 Complex. Cells, 9 (5). p. 1128. ISSN 2073-4409

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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 sufficient 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.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Solé, Laura
Sastre, Daniel
Colomer-Molera, Magalí
Vallejo-Gracia, Albert
Roig, Sara R.
Pérez-Verdaguer, Mireiamip85@pitt.edumip85
Lillo, Pilar
Tamkun, Michael M.
Felipe, Antonio
Date: 2 May 2020
Date Type: Publication
Journal or Publication Title: Cells
Volume: 9
Number: 5
Publisher: MDPI AG
Page Range: p. 1128
DOI or Unique Handle: 10.3390/cells9051128
Schools and Programs: School of Medicine > Cell Biology
Refereed: Yes
Uncontrolled Keywords: potassium channels, immune system, oligomeric complex, regulatory subunits
ISSN: 2073-4409
Official URL:
Funders: Ministerio de Economia y Competitividad, Fondo Europeo de Desarrollo Regional
Article Type: Research Article
Date Deposited: 29 Jun 2021 18:38
Last Modified: 29 Jun 2021 18:38


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