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Endocytosis: A Turnover Mechanism Controlling Ion Channel Function

Ion channels (IChs) are transmembrane proteins that selectively drive ions across membranes. The function of IChs partially relies on their abundance and proper location in the cell, fine-tuned by the delicate balance between secretory, endocytic, and degradative pathways. The disruption of this bal...

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Autores principales: Estadella, Irene, Pedrós-Gámez, Oriol, Colomer-Molera, Magalí, Bosch, Manel, Sorkin, Alexander, Felipe, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463639/
https://www.ncbi.nlm.nih.gov/pubmed/32759790
http://dx.doi.org/10.3390/cells9081833
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author Estadella, Irene
Pedrós-Gámez, Oriol
Colomer-Molera, Magalí
Bosch, Manel
Sorkin, Alexander
Felipe, Antonio
author_facet Estadella, Irene
Pedrós-Gámez, Oriol
Colomer-Molera, Magalí
Bosch, Manel
Sorkin, Alexander
Felipe, Antonio
author_sort Estadella, Irene
collection PubMed
description Ion channels (IChs) are transmembrane proteins that selectively drive ions across membranes. The function of IChs partially relies on their abundance and proper location in the cell, fine-tuned by the delicate balance between secretory, endocytic, and degradative pathways. The disruption of this balance is associated with several diseases, such as Liddle’s and long QT syndromes. Because of the vital role of these proteins in human health and disease, knowledge of ICh turnover is essential. Clathrin-dependent and -independent mechanisms have been the primary mechanisms identified with ICh endocytosis and degradation. Several molecular determinants recognized by the cellular internalization machinery have been discovered. Moreover, specific conditions can trigger the endocytosis of many IChs, such as the activation of certain receptors, hypokalemia, and some drugs. Ligand-dependent receptor activation primarily results in the posttranslational modification of IChs and the recruitment of important mediators, such as β-arrestins and ubiquitin ligases. However, endocytosis is not a final fate. Once internalized into endosomes, IChs are either sorted to lysosomes for degradation or recycled back to the plasma membrane. Rab proteins are crucial participants during these turnover steps. In this review, we describe the major ICh endocytic pathways, the signaling inputs triggering ICh internalization, and the key mediators of this essential cellular process.
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spelling pubmed-74636392020-09-02 Endocytosis: A Turnover Mechanism Controlling Ion Channel Function Estadella, Irene Pedrós-Gámez, Oriol Colomer-Molera, Magalí Bosch, Manel Sorkin, Alexander Felipe, Antonio Cells Review Ion channels (IChs) are transmembrane proteins that selectively drive ions across membranes. The function of IChs partially relies on their abundance and proper location in the cell, fine-tuned by the delicate balance between secretory, endocytic, and degradative pathways. The disruption of this balance is associated with several diseases, such as Liddle’s and long QT syndromes. Because of the vital role of these proteins in human health and disease, knowledge of ICh turnover is essential. Clathrin-dependent and -independent mechanisms have been the primary mechanisms identified with ICh endocytosis and degradation. Several molecular determinants recognized by the cellular internalization machinery have been discovered. Moreover, specific conditions can trigger the endocytosis of many IChs, such as the activation of certain receptors, hypokalemia, and some drugs. Ligand-dependent receptor activation primarily results in the posttranslational modification of IChs and the recruitment of important mediators, such as β-arrestins and ubiquitin ligases. However, endocytosis is not a final fate. Once internalized into endosomes, IChs are either sorted to lysosomes for degradation or recycled back to the plasma membrane. Rab proteins are crucial participants during these turnover steps. In this review, we describe the major ICh endocytic pathways, the signaling inputs triggering ICh internalization, and the key mediators of this essential cellular process. MDPI 2020-08-04 /pmc/articles/PMC7463639/ /pubmed/32759790 http://dx.doi.org/10.3390/cells9081833 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Estadella, Irene
Pedrós-Gámez, Oriol
Colomer-Molera, Magalí
Bosch, Manel
Sorkin, Alexander
Felipe, Antonio
Endocytosis: A Turnover Mechanism Controlling Ion Channel Function
title Endocytosis: A Turnover Mechanism Controlling Ion Channel Function
title_full Endocytosis: A Turnover Mechanism Controlling Ion Channel Function
title_fullStr Endocytosis: A Turnover Mechanism Controlling Ion Channel Function
title_full_unstemmed Endocytosis: A Turnover Mechanism Controlling Ion Channel Function
title_short Endocytosis: A Turnover Mechanism Controlling Ion Channel Function
title_sort endocytosis: a turnover mechanism controlling ion channel function
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463639/
https://www.ncbi.nlm.nih.gov/pubmed/32759790
http://dx.doi.org/10.3390/cells9081833
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