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Two-pore channels affect EGF receptor signaling by receptor trafficking and expression
Two-pore channels (TPCs) are key components for regulating Ca(2+) current from endosomes and lysosomes to the cytosol. This locally restricted Ca(2+) current forms the basis for fusion and fission events between endolysosomal membranes and thereby for intracellular trafficking processes. Here, we st...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887427/ https://www.ncbi.nlm.nih.gov/pubmed/33644717 http://dx.doi.org/10.1016/j.isci.2021.102099 |
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author | Müller, Thomas Grossmann, Sonja Mallmann, Robert Theodor Rommel, Carolin Hein, Lutz Klugbauer, Norbert |
author_facet | Müller, Thomas Grossmann, Sonja Mallmann, Robert Theodor Rommel, Carolin Hein, Lutz Klugbauer, Norbert |
author_sort | Müller, Thomas |
collection | PubMed |
description | Two-pore channels (TPCs) are key components for regulating Ca(2+) current from endosomes and lysosomes to the cytosol. This locally restricted Ca(2+) current forms the basis for fusion and fission events between endolysosomal membranes and thereby for intracellular trafficking processes. Here, we study the function of TPC1 and TPC2 for uptake, recycling, and degradation of epidermal growth factor receptor (EGFR) using a set of TPC knockout cells. RNA sequencing analysis revealed multiple changes in the expression levels of EGFR pathway-related genes in TPC1-deficient cells. We propose that a prolonged presence of activated EGFRs in endolysosomal signaling platforms, caused by genetic inactivation of TPCs, does not only affect EGFR signaling pathways but also increases de novo synthesis of EGFR. Increased basal phospho-c-Jun levels contribute to the high EGFR expression in TPC-deficient cells. Our data point to a role of TPCs not only as important regulators for the EGFR transportation network but also for EGFR-signaling and expression. |
format | Online Article Text |
id | pubmed-7887427 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-78874272021-02-26 Two-pore channels affect EGF receptor signaling by receptor trafficking and expression Müller, Thomas Grossmann, Sonja Mallmann, Robert Theodor Rommel, Carolin Hein, Lutz Klugbauer, Norbert iScience Article Two-pore channels (TPCs) are key components for regulating Ca(2+) current from endosomes and lysosomes to the cytosol. This locally restricted Ca(2+) current forms the basis for fusion and fission events between endolysosomal membranes and thereby for intracellular trafficking processes. Here, we study the function of TPC1 and TPC2 for uptake, recycling, and degradation of epidermal growth factor receptor (EGFR) using a set of TPC knockout cells. RNA sequencing analysis revealed multiple changes in the expression levels of EGFR pathway-related genes in TPC1-deficient cells. We propose that a prolonged presence of activated EGFRs in endolysosomal signaling platforms, caused by genetic inactivation of TPCs, does not only affect EGFR signaling pathways but also increases de novo synthesis of EGFR. Increased basal phospho-c-Jun levels contribute to the high EGFR expression in TPC-deficient cells. Our data point to a role of TPCs not only as important regulators for the EGFR transportation network but also for EGFR-signaling and expression. Elsevier 2021-01-27 /pmc/articles/PMC7887427/ /pubmed/33644717 http://dx.doi.org/10.1016/j.isci.2021.102099 Text en © 2021 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Müller, Thomas Grossmann, Sonja Mallmann, Robert Theodor Rommel, Carolin Hein, Lutz Klugbauer, Norbert Two-pore channels affect EGF receptor signaling by receptor trafficking and expression |
title | Two-pore channels affect EGF receptor signaling by receptor trafficking and expression |
title_full | Two-pore channels affect EGF receptor signaling by receptor trafficking and expression |
title_fullStr | Two-pore channels affect EGF receptor signaling by receptor trafficking and expression |
title_full_unstemmed | Two-pore channels affect EGF receptor signaling by receptor trafficking and expression |
title_short | Two-pore channels affect EGF receptor signaling by receptor trafficking and expression |
title_sort | two-pore channels affect egf receptor signaling by receptor trafficking and expression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887427/ https://www.ncbi.nlm.nih.gov/pubmed/33644717 http://dx.doi.org/10.1016/j.isci.2021.102099 |
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