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Clathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth
The role of Golgi/endosome-localized clathrin adapters in the maintenance of steady-state cell surface epidermal growth factor receptor (EGFR) is not well known. Here, we show that EGFR associates preferentially with both AP-1 and GGA2 in vitro. AP-1 depletion caused a reduction in the EGFR protein...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604998/ https://www.ncbi.nlm.nih.gov/pubmed/34799560 http://dx.doi.org/10.1038/s41389-021-00367-2 |
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author | Uemura, Takefumi Suzuki, Takehiro Dohmae, Naoshi Waguri, Satoshi |
author_facet | Uemura, Takefumi Suzuki, Takehiro Dohmae, Naoshi Waguri, Satoshi |
author_sort | Uemura, Takefumi |
collection | PubMed |
description | The role of Golgi/endosome-localized clathrin adapters in the maintenance of steady-state cell surface epidermal growth factor receptor (EGFR) is not well known. Here, we show that EGFR associates preferentially with both AP-1 and GGA2 in vitro. AP-1 depletion caused a reduction in the EGFR protein by promoting its lysosomal degradation. Triple immunofluorescence microscopy and proximity ligation assays demonstrated that the interaction of EGFR with AP-1 or GGA2 occurred more frequently in Rab11-positive recycling endosomes than in Rab5-positive early endosomes. Biochemical recycling assay revealed that the depletion of AP-1 or GGA2 significantly suppressed EGFR recycling to the plasma membrane regardless of the EGF stimulation. Depletion of AP-1 or GGA2 also reduced cell contents of other tyrosine kinases, MET and ErbB4, and therefore, suppressed the growth of H1975 cancer cells in culture and xenograft model. Moreover, AP-1 was expressed in endosomes at higher levels in some cancer tissues. Collectively, these results suggest that AP-1 and GGA2 function in recycling endosomes to retrieve endocytosed EGFR, thereby sustaining its cell surface expression and, consequently, cancer cell growth. |
format | Online Article Text |
id | pubmed-8604998 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-86049982021-12-03 Clathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth Uemura, Takefumi Suzuki, Takehiro Dohmae, Naoshi Waguri, Satoshi Oncogenesis Article The role of Golgi/endosome-localized clathrin adapters in the maintenance of steady-state cell surface epidermal growth factor receptor (EGFR) is not well known. Here, we show that EGFR associates preferentially with both AP-1 and GGA2 in vitro. AP-1 depletion caused a reduction in the EGFR protein by promoting its lysosomal degradation. Triple immunofluorescence microscopy and proximity ligation assays demonstrated that the interaction of EGFR with AP-1 or GGA2 occurred more frequently in Rab11-positive recycling endosomes than in Rab5-positive early endosomes. Biochemical recycling assay revealed that the depletion of AP-1 or GGA2 significantly suppressed EGFR recycling to the plasma membrane regardless of the EGF stimulation. Depletion of AP-1 or GGA2 also reduced cell contents of other tyrosine kinases, MET and ErbB4, and therefore, suppressed the growth of H1975 cancer cells in culture and xenograft model. Moreover, AP-1 was expressed in endosomes at higher levels in some cancer tissues. Collectively, these results suggest that AP-1 and GGA2 function in recycling endosomes to retrieve endocytosed EGFR, thereby sustaining its cell surface expression and, consequently, cancer cell growth. Nature Publishing Group UK 2021-11-19 /pmc/articles/PMC8604998/ /pubmed/34799560 http://dx.doi.org/10.1038/s41389-021-00367-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Uemura, Takefumi Suzuki, Takehiro Dohmae, Naoshi Waguri, Satoshi Clathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth |
title | Clathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth |
title_full | Clathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth |
title_fullStr | Clathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth |
title_full_unstemmed | Clathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth |
title_short | Clathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth |
title_sort | clathrin adapters ap-1 and gga2 support expression of epidermal growth factor receptor for cell growth |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604998/ https://www.ncbi.nlm.nih.gov/pubmed/34799560 http://dx.doi.org/10.1038/s41389-021-00367-2 |
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