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Dynein-mediated trafficking negatively regulates LET-23 EGFR signaling

Epidermal growth factor receptor (EGFR) signaling is essential for animal development, and increased signaling underlies many human cancers. Identifying the genes and cellular processes that regulate EGFR signaling in vivo will help to elucidate how this pathway can become inappropriately activated....

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Autores principales: Skorobogata, Olga, Meng, Jassy, Gauthier, Kimberley, Rocheleau, Christian E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5170559/
https://www.ncbi.nlm.nih.gov/pubmed/27654944
http://dx.doi.org/10.1091/mbc.E15-11-0757
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author Skorobogata, Olga
Meng, Jassy
Gauthier, Kimberley
Rocheleau, Christian E.
author_facet Skorobogata, Olga
Meng, Jassy
Gauthier, Kimberley
Rocheleau, Christian E.
author_sort Skorobogata, Olga
collection PubMed
description Epidermal growth factor receptor (EGFR) signaling is essential for animal development, and increased signaling underlies many human cancers. Identifying the genes and cellular processes that regulate EGFR signaling in vivo will help to elucidate how this pathway can become inappropriately activated. Caenorhabditis elegans vulva development provides an in vivo model to genetically dissect EGFR signaling. Here we identified a mutation in dhc-1, the heavy chain of the cytoplasmic dynein minus end–directed microtubule motor, in a genetic screen for regulators of EGFR signaling. Despite the many cellular functions of dynein, DHC-1 is a strong negative regulator of EGFR signaling during vulva induction. DHC-1 is required in the signal-receiving cell and genetically functions upstream or in parallel to LET-23 EGFR. LET-23 EGFR accumulates in cytoplasmic foci in dhc-1 mutants, consistent with mammalian cell studies in which dynein is shown to regulate late endosome trafficking of EGFR with the Rab7 GTPase. However, we found different distributions of LET-23 EGFR foci in rab-7 versus dhc-1 mutants, suggesting that dynein functions at an earlier step of LET-23 EGFR trafficking to the lysosome than RAB-7. Our results demonstrate an in vivo role for dynein in limiting LET-23 EGFR signaling via endosomal trafficking.
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spelling pubmed-51705592017-01-30 Dynein-mediated trafficking negatively regulates LET-23 EGFR signaling Skorobogata, Olga Meng, Jassy Gauthier, Kimberley Rocheleau, Christian E. Mol Biol Cell Articles Epidermal growth factor receptor (EGFR) signaling is essential for animal development, and increased signaling underlies many human cancers. Identifying the genes and cellular processes that regulate EGFR signaling in vivo will help to elucidate how this pathway can become inappropriately activated. Caenorhabditis elegans vulva development provides an in vivo model to genetically dissect EGFR signaling. Here we identified a mutation in dhc-1, the heavy chain of the cytoplasmic dynein minus end–directed microtubule motor, in a genetic screen for regulators of EGFR signaling. Despite the many cellular functions of dynein, DHC-1 is a strong negative regulator of EGFR signaling during vulva induction. DHC-1 is required in the signal-receiving cell and genetically functions upstream or in parallel to LET-23 EGFR. LET-23 EGFR accumulates in cytoplasmic foci in dhc-1 mutants, consistent with mammalian cell studies in which dynein is shown to regulate late endosome trafficking of EGFR with the Rab7 GTPase. However, we found different distributions of LET-23 EGFR foci in rab-7 versus dhc-1 mutants, suggesting that dynein functions at an earlier step of LET-23 EGFR trafficking to the lysosome than RAB-7. Our results demonstrate an in vivo role for dynein in limiting LET-23 EGFR signaling via endosomal trafficking. The American Society for Cell Biology 2016-11-15 /pmc/articles/PMC5170559/ /pubmed/27654944 http://dx.doi.org/10.1091/mbc.E15-11-0757 Text en © 2016 Skorobogata, Meng, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Skorobogata, Olga
Meng, Jassy
Gauthier, Kimberley
Rocheleau, Christian E.
Dynein-mediated trafficking negatively regulates LET-23 EGFR signaling
title Dynein-mediated trafficking negatively regulates LET-23 EGFR signaling
title_full Dynein-mediated trafficking negatively regulates LET-23 EGFR signaling
title_fullStr Dynein-mediated trafficking negatively regulates LET-23 EGFR signaling
title_full_unstemmed Dynein-mediated trafficking negatively regulates LET-23 EGFR signaling
title_short Dynein-mediated trafficking negatively regulates LET-23 EGFR signaling
title_sort dynein-mediated trafficking negatively regulates let-23 egfr signaling
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5170559/
https://www.ncbi.nlm.nih.gov/pubmed/27654944
http://dx.doi.org/10.1091/mbc.E15-11-0757
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