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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-08-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/9/8/1833 |
| _version_ | 1797560319022727168 |
|---|---|
| author | Irene Estadella Oriol Pedrós-Gámez Magalí Colomer-Molera Manel Bosch Alexander Sorkin Antonio Felipe |
| author_facet | Irene Estadella Oriol Pedrós-Gámez Magalí Colomer-Molera Manel Bosch Alexander Sorkin Antonio Felipe |
| author_sort | Irene Estadella |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T17:58:45Z |
| format | Article |
| id | doaj.art-5230e6c3776f44f0b9b10fb9fbaaa366 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T17:58:45Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-5230e6c3776f44f0b9b10fb9fbaaa3662023-11-20T09:03:33ZengMDPI AGCells2073-44092020-08-0198183310.3390/cells9081833Endocytosis: A Turnover Mechanism Controlling Ion Channel FunctionIrene Estadella0Oriol Pedrós-Gámez1Magalí Colomer-Molera2Manel Bosch3Alexander Sorkin4Antonio Felipe5Molecular Physiology Laboratory, Departament de Bioquímica i Biomedicina Molecular, Institut de Biomedicina (IBUB), Universitat de Barcelona, 08028 Barcelona, SpainMolecular Physiology Laboratory, Departament de Bioquímica i Biomedicina Molecular, Institut de Biomedicina (IBUB), Universitat de Barcelona, 08028 Barcelona, SpainMolecular Physiology Laboratory, Departament de Bioquímica i Biomedicina Molecular, Institut de Biomedicina (IBUB), Universitat de Barcelona, 08028 Barcelona, SpainMolecular Physiology Laboratory, Departament de Bioquímica i Biomedicina Molecular, Institut de Biomedicina (IBUB), Universitat de Barcelona, 08028 Barcelona, SpainDepartment of Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USAMolecular Physiology Laboratory, Departament de Bioquímica i Biomedicina Molecular, Institut de Biomedicina (IBUB), Universitat de Barcelona, 08028 Barcelona, SpainIon 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.https://www.mdpi.com/2073-4409/9/8/1833ion channelsendocytosisturnoverubiquitination |
| spellingShingle | Irene Estadella Oriol Pedrós-Gámez Magalí Colomer-Molera Manel Bosch Alexander Sorkin Antonio Felipe Endocytosis: A Turnover Mechanism Controlling Ion Channel Function Cells ion channels endocytosis turnover ubiquitination |
| 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 | ion channels endocytosis turnover ubiquitination |
| url | https://www.mdpi.com/2073-4409/9/8/1833 |
| work_keys_str_mv | AT ireneestadella endocytosisaturnovermechanismcontrollingionchannelfunction AT oriolpedrosgamez endocytosisaturnovermechanismcontrollingionchannelfunction AT magalicolomermolera endocytosisaturnovermechanismcontrollingionchannelfunction AT manelbosch endocytosisaturnovermechanismcontrollingionchannelfunction AT alexandersorkin endocytosisaturnovermechanismcontrollingionchannelfunction AT antoniofelipe endocytosisaturnovermechanismcontrollingionchannelfunction |