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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....
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2016
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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. |
format | Online Article Text |
id | pubmed-5170559 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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