Calmodulin-dependent KCNE4 dimerization controls membrane targeting.
The voltage-dependent potassium channel Kv1.3 participates in the immune response. Kv1.3 is essential in diferent cellular functions, such as proliferation, activation and apoptosis. Because aberrant expression of Kv1.3 is linked to autoimmune diseases, fne-tuning its function is crucial for leukocy...
| Autores: | , , , , , , , , , |
|---|---|
| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Recursos: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/186238 |
| Acesso em linha: | https://hdl.handle.net/2445/186238 |
| Access Level: | acceso abierto |
| Palavra-chave: | Malalties autoimmunitàries Canals de potassi Reticle endoplasmàtic Autoimmune diseases Potassium channels Endoplasmic reticulum |
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Calmodulin-dependent KCNE4 dimerization controls membrane targeting.Roig, Sara R.Solé, LauraCassinelli, SilviaColomer-Molera, MagalíSastre Martinez, DanielSerrano-Novillo, ClaraSerrano-Albarrás, AntonioLillo, M. PilarTamkun, Michael M.Felipe Campo, AntonioMalalties autoimmunitàriesCanals de potassiReticle endoplasmàticAutoimmune diseasesPotassium channelsEndoplasmic reticulumThe voltage-dependent potassium channel Kv1.3 participates in the immune response. Kv1.3 is essential in diferent cellular functions, such as proliferation, activation and apoptosis. Because aberrant expression of Kv1.3 is linked to autoimmune diseases, fne-tuning its function is crucial for leukocyte physiology. Regulatory KCNE subunits are expressed in the immune system, and KCNE4 specifcally tightly regulates Kv1.3. KCNE4 modulates Kv1.3 currents slowing activation, accelerating inactivation and retaining the channel at the endoplasmic reticulum (ER), thereby altering its membrane localization. In addition, KCNE4 genomic variants are associated with immune pathologies. Therefore, an in-depth knowledge of KCNE4 function is extremely relevant for understanding immune system physiology. We demonstrate that KCNE4 dimerizes, which is unique among KCNE regulatory peptide family members. Furthermore, the juxtamembrane tetraleucine carboxyl-terminal domain of KCNE4 is a structural platform in which Kv1.3, Ca2+/calmodulin (CaM) and dimerizing KCNE4 compete for multiple interaction partners. CaM-dependent KCNE4 dimerization controls KCNE4 membrane targeting and modulates its interaction with Kv1.3. KCNE4, which is highly retained at the ER, contains an important ER retention motif near the tetraleucine motif. Upon escaping the ER in a CaM-dependent pattern, KCNE4 follows a COP-II-dependent forward trafcking mechanism. Therefore, CaM, an essential signaling molecule that controls the dimerization and membrane targeting of KCNE4, modulates the KCNE4-dependent regulation of Kv1.3, which in turn fne-tunes leukocyte physiology.Nature Publishing Group2022202220212022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion16 p.application/pdfhttps://hdl.handle.net/2445/186238Articles publicats en revistes (Bioquímica i Biomedicina Molecular)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1038/s41598-021-93562-5Scientific Reports, 2021, vol. 11, num. 1, p. 14046https://doi.org/10.1038/s41598-021-93562-5cc-by (c) Roig, Sara R. et al., 2021https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1862382026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Calmodulin-dependent KCNE4 dimerization controls membrane targeting. |
| title |
Calmodulin-dependent KCNE4 dimerization controls membrane targeting. |
| spellingShingle |
Calmodulin-dependent KCNE4 dimerization controls membrane targeting. Roig, Sara R. Malalties autoimmunitàries Canals de potassi Reticle endoplasmàtic Autoimmune diseases Potassium channels Endoplasmic reticulum |
| title_short |
Calmodulin-dependent KCNE4 dimerization controls membrane targeting. |
| title_full |
Calmodulin-dependent KCNE4 dimerization controls membrane targeting. |
| title_fullStr |
Calmodulin-dependent KCNE4 dimerization controls membrane targeting. |
| title_full_unstemmed |
Calmodulin-dependent KCNE4 dimerization controls membrane targeting. |
| title_sort |
Calmodulin-dependent KCNE4 dimerization controls membrane targeting. |
| dc.creator.none.fl_str_mv |
Roig, Sara R. Solé, Laura Cassinelli, Silvia Colomer-Molera, Magalí Sastre Martinez, Daniel Serrano-Novillo, Clara Serrano-Albarrás, Antonio Lillo, M. Pilar Tamkun, Michael M. Felipe Campo, Antonio |
| author |
Roig, Sara R. |
| author_facet |
Roig, Sara R. Solé, Laura Cassinelli, Silvia Colomer-Molera, Magalí Sastre Martinez, Daniel Serrano-Novillo, Clara Serrano-Albarrás, Antonio Lillo, M. Pilar Tamkun, Michael M. Felipe Campo, Antonio |
| author_role |
author |
| author2 |
Solé, Laura Cassinelli, Silvia Colomer-Molera, Magalí Sastre Martinez, Daniel Serrano-Novillo, Clara Serrano-Albarrás, Antonio Lillo, M. Pilar Tamkun, Michael M. Felipe Campo, Antonio |
| author2_role |
author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Malalties autoimmunitàries Canals de potassi Reticle endoplasmàtic Autoimmune diseases Potassium channels Endoplasmic reticulum |
| topic |
Malalties autoimmunitàries Canals de potassi Reticle endoplasmàtic Autoimmune diseases Potassium channels Endoplasmic reticulum |
| description |
The voltage-dependent potassium channel Kv1.3 participates in the immune response. Kv1.3 is essential in diferent cellular functions, such as proliferation, activation and apoptosis. Because aberrant expression of Kv1.3 is linked to autoimmune diseases, fne-tuning its function is crucial for leukocyte physiology. Regulatory KCNE subunits are expressed in the immune system, and KCNE4 specifcally tightly regulates Kv1.3. KCNE4 modulates Kv1.3 currents slowing activation, accelerating inactivation and retaining the channel at the endoplasmic reticulum (ER), thereby altering its membrane localization. In addition, KCNE4 genomic variants are associated with immune pathologies. Therefore, an in-depth knowledge of KCNE4 function is extremely relevant for understanding immune system physiology. We demonstrate that KCNE4 dimerizes, which is unique among KCNE regulatory peptide family members. Furthermore, the juxtamembrane tetraleucine carboxyl-terminal domain of KCNE4 is a structural platform in which Kv1.3, Ca2+/calmodulin (CaM) and dimerizing KCNE4 compete for multiple interaction partners. CaM-dependent KCNE4 dimerization controls KCNE4 membrane targeting and modulates its interaction with Kv1.3. KCNE4, which is highly retained at the ER, contains an important ER retention motif near the tetraleucine motif. Upon escaping the ER in a CaM-dependent pattern, KCNE4 follows a COP-II-dependent forward trafcking mechanism. Therefore, CaM, an essential signaling molecule that controls the dimerization and membrane targeting of KCNE4, modulates the KCNE4-dependent regulation of Kv1.3, which in turn fne-tunes leukocyte physiology. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021 2022 2022 2022 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/186238 |
| url |
https://hdl.handle.net/2445/186238 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/10.1038/s41598-021-93562-5 Scientific Reports, 2021, vol. 11, num. 1, p. 14046 https://doi.org/10.1038/s41598-021-93562-5 |
| dc.rights.none.fl_str_mv |
cc-by (c) Roig, Sara R. et al., 2021 https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
cc-by (c) Roig, Sara R. et al., 2021 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
| dc.format.none.fl_str_mv |
16 p. application/pdf |
| dc.publisher.none.fl_str_mv |
Nature Publishing Group |
| publisher.none.fl_str_mv |
Nature Publishing Group |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Bioquímica i Biomedicina Molecular) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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