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Endocytosis: A Turnover Mechanism Controlling Ion Channel Function

Estadella, Irene and Pedrós-Gámez, Oriol and Colomer-Molera, Magalí and Bosch, Manel and Sorkin, Alexander and Felipe, Antonio (2020) Endocytosis: A Turnover Mechanism Controlling Ion Channel Function. Cells, 9 (8). p. 1833. ISSN 2073-4409

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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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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Estadella, Irene
Pedrós-Gámez, Oriol
Colomer-Molera, Magalí
Bosch, Manel
Sorkin, Alexandersorkin@pitt.edusorkin
Felipe, Antonio
Date: 4 August 2020
Date Type: Publication
Journal or Publication Title: Cells
Volume: 9
Number: 8
Publisher: MDPI AG
Page Range: p. 1833
DOI or Unique Handle: 10.3390/cells9081833
Schools and Programs: School of Medicine > Cell Biology
Refereed: Yes
Uncontrolled Keywords: ion channels, endocytosis, turnover, ubiquitination
ISSN: 2073-4409
Official URL:
Funders: Ministerio de Ciencia e Innovación, Fondo Europeo de Desarrollo Regional, National Institute of General Medical Sciences, National Cancer Institute, National Institute on Drug Abuse, National Science Foundation
Article Type: Review
Date Deposited: 28 Jun 2021 19:11
Last Modified: 28 Jun 2021 19:11


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