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An In Vivo EGF Receptor Localization Screen in C. elegans Identifies the Ezrin Homolog ERM-1 as a Temporal Regulator of Signaling

The subcellular localization of the epidermal growth factor receptor (EGFR) in polarized epithelial cells profoundly affects the activity of the intracellular signaling pathways activated after EGF ligand binding. Therefore, changes in EGFR localization and signaling are implicated in various human...

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Autores principales: Haag, Andrea, Gutierrez, Peter, Bühler, Alessandra, Walser, Michael, Yang, Qiutan, Langouët, Maeva, Kradolfer, David, Fröhli, Erika, Herrmann, Christina J., Hajnal, Alex, Escobar-Restrepo, Juan M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006739/
https://www.ncbi.nlm.nih.gov/pubmed/24785082
http://dx.doi.org/10.1371/journal.pgen.1004341
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author Haag, Andrea
Gutierrez, Peter
Bühler, Alessandra
Walser, Michael
Yang, Qiutan
Langouët, Maeva
Kradolfer, David
Fröhli, Erika
Herrmann, Christina J.
Hajnal, Alex
Escobar-Restrepo, Juan M.
author_facet Haag, Andrea
Gutierrez, Peter
Bühler, Alessandra
Walser, Michael
Yang, Qiutan
Langouët, Maeva
Kradolfer, David
Fröhli, Erika
Herrmann, Christina J.
Hajnal, Alex
Escobar-Restrepo, Juan M.
author_sort Haag, Andrea
collection PubMed
description The subcellular localization of the epidermal growth factor receptor (EGFR) in polarized epithelial cells profoundly affects the activity of the intracellular signaling pathways activated after EGF ligand binding. Therefore, changes in EGFR localization and signaling are implicated in various human diseases, including different types of cancer. We have performed the first in vivo EGFR localization screen in an animal model by observing the expression of the EGFR ortholog LET-23 in the vulval epithelium of live C. elegans larvae. After systematically testing all genes known to produce an aberrant vulval phenotype, we have identified 81 genes regulating various aspects of EGFR localization and expression. In particular, we have found that ERM-1, the sole C. elegans Ezrin/Radixin/Moesin homolog, regulates EGFR localization and signaling in the vulval cells. ERM-1 interacts with the EGFR at the basolateral plasma membrane in a complex distinct from the previously identified LIN-2/LIN-7/LIN-10 receptor localization complex. We propose that ERM-1 binds to and sequesters basolateral LET-23 EGFR in an actin-rich inactive membrane compartment to restrict receptor mobility and signaling. In this manner, ERM-1 prevents the immediate activation of the entire pool of LET-23 EGFR and permits the generation of a long-lasting inductive signal. The regulation of receptor localization thus serves to fine-tune the temporal activation of intracellular signaling pathways.
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spelling pubmed-40067392014-05-09 An In Vivo EGF Receptor Localization Screen in C. elegans Identifies the Ezrin Homolog ERM-1 as a Temporal Regulator of Signaling Haag, Andrea Gutierrez, Peter Bühler, Alessandra Walser, Michael Yang, Qiutan Langouët, Maeva Kradolfer, David Fröhli, Erika Herrmann, Christina J. Hajnal, Alex Escobar-Restrepo, Juan M. PLoS Genet Research Article The subcellular localization of the epidermal growth factor receptor (EGFR) in polarized epithelial cells profoundly affects the activity of the intracellular signaling pathways activated after EGF ligand binding. Therefore, changes in EGFR localization and signaling are implicated in various human diseases, including different types of cancer. We have performed the first in vivo EGFR localization screen in an animal model by observing the expression of the EGFR ortholog LET-23 in the vulval epithelium of live C. elegans larvae. After systematically testing all genes known to produce an aberrant vulval phenotype, we have identified 81 genes regulating various aspects of EGFR localization and expression. In particular, we have found that ERM-1, the sole C. elegans Ezrin/Radixin/Moesin homolog, regulates EGFR localization and signaling in the vulval cells. ERM-1 interacts with the EGFR at the basolateral plasma membrane in a complex distinct from the previously identified LIN-2/LIN-7/LIN-10 receptor localization complex. We propose that ERM-1 binds to and sequesters basolateral LET-23 EGFR in an actin-rich inactive membrane compartment to restrict receptor mobility and signaling. In this manner, ERM-1 prevents the immediate activation of the entire pool of LET-23 EGFR and permits the generation of a long-lasting inductive signal. The regulation of receptor localization thus serves to fine-tune the temporal activation of intracellular signaling pathways. Public Library of Science 2014-05-01 /pmc/articles/PMC4006739/ /pubmed/24785082 http://dx.doi.org/10.1371/journal.pgen.1004341 Text en © 2014 Haag et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Haag, Andrea
Gutierrez, Peter
Bühler, Alessandra
Walser, Michael
Yang, Qiutan
Langouët, Maeva
Kradolfer, David
Fröhli, Erika
Herrmann, Christina J.
Hajnal, Alex
Escobar-Restrepo, Juan M.
An In Vivo EGF Receptor Localization Screen in C. elegans Identifies the Ezrin Homolog ERM-1 as a Temporal Regulator of Signaling
title An In Vivo EGF Receptor Localization Screen in C. elegans Identifies the Ezrin Homolog ERM-1 as a Temporal Regulator of Signaling
title_full An In Vivo EGF Receptor Localization Screen in C. elegans Identifies the Ezrin Homolog ERM-1 as a Temporal Regulator of Signaling
title_fullStr An In Vivo EGF Receptor Localization Screen in C. elegans Identifies the Ezrin Homolog ERM-1 as a Temporal Regulator of Signaling
title_full_unstemmed An In Vivo EGF Receptor Localization Screen in C. elegans Identifies the Ezrin Homolog ERM-1 as a Temporal Regulator of Signaling
title_short An In Vivo EGF Receptor Localization Screen in C. elegans Identifies the Ezrin Homolog ERM-1 as a Temporal Regulator of Signaling
title_sort in vivo egf receptor localization screen in c. elegans identifies the ezrin homolog erm-1 as a temporal regulator of signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006739/
https://www.ncbi.nlm.nih.gov/pubmed/24785082
http://dx.doi.org/10.1371/journal.pgen.1004341
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